Diagnosis and Management of Acquired Aplastic Anemia: Consensus Statement of Indian Academy of Pediatrics

Justification: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). Process: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. Recommendations: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophosphamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.

Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up / Trasplante de células progenitoras hematopoyéticas en un paciente con osteopetrosis y mutación en CLCN7: seguimiento a largo plazo

Abstract Background: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. Case report: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related donor and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. Conclusions: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.

Resumen Introducción: La osteopetrosis es una displasia ósea hereditaria poco común, caracterizada por una actividad osteoclástica deficiente que aumenta la densidad mineral ósea. Se considera que el trasplante de células progenitoras hematopoyéticas (TCPH) puede revertir las anormalidades esqueléticas y restaurar la hematopoyesis. Caso clínico: Se presenta el caso de un paciente de sexo masculino, de 3 años y 2 meses de edad, con diagnóstico tardío de osteopetrosis. Se realizó un TCPH alogénico de donador relacionado 100% compatible con médula ósea. Se utilizaron un régimen de acondicionamiento mieloablativo y una dosis celular de CD34 de 4.7 × 107/kg de peso. En el postrasplante temprano, el paciente desarrolló complicaciones como neumonitis, hipercalcemia e hiperfosfatemia. Con un injerto granulocítico adecuado y quimerismo del 100% se consideró un trasplante exitoso. Sin embargo, el paciente presentó retraso en el injerto plaquetario, por lo que se administró factor estimulante de plaquetas por 6 meses. Actualmente el paciente se encuentra libre de enfermedad, en seguimiento ambulatorio, sin datos de enfermedad del injerto contra el hospedero y con pruebas de neurodesarrollo sin deterioro neurológico progresivo. Conclusiones: La osteopetrosis es una enfermedad infantil que requiere una sospecha clínica y un diagnóstico temprano, ya que es necesario un TCPH a corta edad como tratamiento para evitar la progresión de la enfermedad y el deterioro de las funciones neurosensoriales, hematológicas y endocrinológicas que puede derivar en la defunción del paciente.

COVID-19 in hematology: data from a hematologic and transplant unit

ABSTRACT During the COVID-19 pandemic, special attention has been addressed in cancer care to mitigate the impact on the patient's prognosis. We addressed our preparation to face COVID-19 pandemic in a Hematological and Stem Cell Transplant Unit in Brazil during the first two months of COVID-19 pandemic and described COVID-19 cases in patients and health care workers (HCW). Modifications in daily routines included a separation of area and professionals, SARS-CoV-2 screening protocols, and others. A total of 47 patients and 54 HCW were tested for COVID-19, by PCR-SARS-CoV-2. We report 11 cases of COVID-19 in hematological patients (including 2 post stem cell transplant) and 28 cases in HCW. Hematological cases were most severe or moderate and presented with several poor risk factors. Among HCW, COVID-19 were mostly mild, and all recovered without hospitalization. A cluster was observed among HCW. Despite a decrease in the number of procedures, the Transplant Program performed 8 autologous and 4 allogeneic SCT during the period, and 49 onco-hematological patients were admitted to continuing their treatments. Although we observed a high frequency of COVID-19 among patients and HCW, showing that SARS-CoV-2 is disseminated in Brazil, hematological patients were safely treated during pandemic times.

Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos / Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation

Resumen Introducción: Los niños que reciben trasplante de precursores hematopoyéticos (TPH) pueden presentar infecciones respiratorias virales (IRV) durante episodios febriles. Los datos sobre su evolución clínica son escasos, así como la comparación de ellos con infecciones bacterianas (IB). Objetivo: Caracterizar la evolución clínica de pacientes con IRV, en comparación con IB en niños con TPH, cursando un episodio febril. Método: Estudio prospectivo en pacientes ≤ 18 años con cáncer y TPH ingresados por fiebre en el Hospital Luis Calvo Mackenna (2016-2019). Se realizó evaluación clínica y de laboratorio: hemocultivos, RPC para patógenos respiratorios (Filmarray®), cuantificación viral y medición de citoquinas en muestra nasal (Luminex®, 38 citoquinas). Se compararon los grupos IRV, IB y los de etiología no precisada (ENP) en relación con: infección respiratoria aguda (IRA), citoquinas nasales, ingreso a UCI, necesidad de ventilación mecánica, mortalidad y suspensión de antimicrobianos. Resultados: De 56 episodios febriles, 35 fueron IRV, 12 IB y 9 de ENP. Mediana de edad fue 8,5 años, 62% masculino. Un 94% de los casos IRV presentó IRA sintomática, versus 33% en los grupos IB y ENP (p < 0,001), con IRA baja en 69% de las IRV (p < 0,001). Rinovirus (54%) y coronavirus (15%) fueron las etiologías más frecuentemente detectadas. No hubo diferencias en citoquinas nasales entre los grupos IRV e IB. Ingreso a UCI: 11% del grupo IRV, 17% de IB y 11% de ENP (p = 0,88). Requirieron ventilación mecánica sólo 2 pacientes (p = 0,37) sin fallecimiento. Tras la detección viral respiratoria por RPC, se suspendió antimicrobianos en 26% de los casos con IRV (p = 0,04). Conclusión: Las IRV son frecuentes en niños con TPH y episodios febriles. La detección viral podría optimizar y racionalizar el uso de antimicrobianos en esta población.

Abstract Background: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. Aim: To determine clinical outcome of RVI, compared to BI in children with HSCT. Methods: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. Results: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). Conclusion: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience

BACKGROUND: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging.METHODS: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37).RESULTS: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib.CONCLUSION: Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Sobrecarga de cuidadores familiares de crianças e adolescentes em pós-transplante de células-tronco hematopoéticas imediato / Burden of family caregivers of children and adolescents in post-hematopoietic stem cell transplantation

Resumo: O objetivo deste trabalho foi avaliar a sobrecarga de cuidadores familiares de crianças e adolescentes no pós-transplante de células-tronco hematopoéticas imediato. Trata-se de um estudo de natureza quantitativa, do tipo analítico e transversal, vinculado ao projeto Construindo processos de cuidado na interface do cuidar em situações de enfermidade grave inserido na linha de pesquisa Processo de cuidar em saúde e enfermagem, realizado em duas instituições de saúde - um complexo hospitalar de ensino, de nível terciário, atendendo a casos de médio e grave risco, e um hospital geral de nível terciário, ambos de Curitiba, Paraná -, escolhidas nesta modalidade de tratamento. A amostra foi composta por 31 cuidadores de crianças e adolescentes no pós-transplante imediato e a coleta de dados foi realizada entre outubro de 2018 e junho de 2019. Foram caracterizados o perfil sociodemográfico dos cuidadores e o perfil clínico das crianças e adolescentes, por meio de questionários elaborados pela autora, e avaliada a sobrecarga do cuidador, pela caregiver burden scale. Para a análise dos dados, utilizaram-se a estatística descritiva, o teste não paramétrico de Mann-Whitney, o teste não paramétrico de Kruskal-Wallis e a correlação de Spearman. Os resultados evidenciaram a prevalência de cuidadores do sexo feminino (93,5%), mães (87,1%), casadas (41,9%), desempregadas (77,4%), recebendo benefícios sociais (51,6%) e residindo em casa de apoio (58,1%). As crianças e adolescentes eram do sexo masculino, idade variando de zero a 16 anos, com diagnóstico predominante de anemia de Fanconi e leucemia linfoide aguda. Os dados revelaram um escore global no valor de 2,4/4, sendo os domínios com maiores escores: tensão geral e decepção, ambos com 2,8/4. Na análise, houve correlação entre esses domínios, bem como entre a variável "ocupação" e o domínio "decepção". A sobrecarga subjetiva neste estudo relacionou-se com o significado de que o cuidar gera impacto positivo ou negativo no cuidado. Conclui-se que a sobrecarga do cuidado repercute nas diversas áreas da vida dos cuidadores, sendo o cuidar no domicílio um desafio para o familiar, um cuidar solitário e desgastante. A partir da avaliação da sobrecarga, será possível ter subsídios para a elaboração de ações em saúde que incluam o familiar no cuidado multidisciplinar.

Abstract: The objective of this research was to evaluate the overload of family caregivers of children and adolescents in immediate post-hematopoietic stem cell transplant. It is a quantitative study of analytical and traverse type, linked to the project Building care processes at the interface of care in situations of serious illness inserted in the research line Care process in health and nursing, accomplished in two health institutions (a teaching hospital compound of tertiary level assisting to cases of medium and serious risk, and a general hospital of tertiary level, both of Curitiba, Paraná), chosen in this treatment modality. The sample was composed by 31 caregivers of children and adolescents in the immediate post-transplant and the data collection was accomplished between October of 2018 and June of 2019. The caregivers social-demographic profile and the children and adolescents clinical profile were characterized through questionnaires elaborated by the author, and the caregivers overload was appraised using the caregiver burden scale. For the data analysis, the descriptive statistics, the Mann-Whitney U test, the Kruskal-Wallis test and the Spearman correlation were used. The results evidenced the prevalence of female caregivers (93.5%), mothers (87.1%), married (41.9%) and unemployed women (77.4%), receiving social benefits (51.6%), and living in support home (58.1%). The children and adolescents were male, with age varying from zero to 16 years old, and the predominant diagnosis was Fanconi anaemia and acute lymphoblastic leukemia. The data revealed a global score of 2.4/4, being the domains with larger scores: general tension and deception, both with 2.8/4. In the analysis, there was correlation among those domains, as well as among occupation and deception. The subjective overload in this study linked with the meaning that taking care generates positive or negative impact in care . In conclusion, the overload in care echoes in several areas of the caregivers' life, being the home taking care a lonely and stressful challenge for the relative. From the evaluation of the overload, it will be possible to have subsidies for the elaboration of actions in health that include the relative in the multidisciplinary care.

Trasplante de progenitores hematopoyéticos autólogo en gammapatías monoclonales: primeros resultados del Hospital "Hermanos Ameijeiras" / Autologous stem cell transplantation in monoclonal gammopathies: first results from the "Hermanos Ameijeiras" Hospital

Introducción: Los avances en el manejo del mieloma múltiple (MM) durante los últimos años incluyen la incorporación del trasplante de progenitores hematopoyéticos autólogo (TPHa) a la estrategia de tratamiento de estos pacientes. Objetivo: Dar a conocer los primeros resultados en el hospital Hermanos Ameijeiras (HHA) con la aplicación del TPHa en pacientes con gammapatías monoclonales (GM), empleando las altas dosis de melfalán (AD-Mel) como tratamiento acondicionante (TA) y su impacto en la sobrevida global (SG). Métodos: Se hizo un estudio retrospectivo de todos los pacientes con GM sometidos a TPHa en el Servicio de Hematología del HHA en el período comprendido entre 2009 y 2018. La muestra final comprendió 14 casos. Resultados: La edad promedio fue de 53,5 años; la mayoría tenía como diagnóstico MM (85,7 por ciento) y todos ellos debutaron en estadio III de Durie-Salmon; como TA el 64,2 por ciento recibió AD-mel, en dosis de 200 mg/m2. La recuperación de las cifras de neutrófilos y plaquetas ocurrieron como promedio a los 11,4 y 12 días, respectivamente. La mortalidad relacionada con el trasplante (MRT) al día +30 fue del 7,1 por ciento. La probabilidad de SG a los 2 años fue superior al 90 por ciento y a los 5 años del 68 por ciento. Conclusiones: Se comprobó que la realización del TPHa con el empleo de AD-Mel como TA en pacientes con GM es un proceder realizable en nuestro país con una MRT relativamente baja. Se logró demostrar que la inclusión del TPH en el tratamiento mejora considerablemente las expectativas de sobrevida de estos pacientes(AU)

Introduction: The recent advances in the management of multiple myeloma (MM) during the last years have included the autologous hematopoietic stem cell transplantation (auto-HSCT) to the treatment strategy of these patients. Objective: To present the first results in the Hermanos Ameijeiras hospital (HAH) with the application of auto-HSCT in patients with monoclonal gammopathies (MG) using high doses of melphalan (HD-Mel) as conditioning regimen (CR) and its impacton overall survival (OS). Methods: A retrospective study of all patients with MG who underwent auto-HSCT in the Hematology Service of the HAH in the period between 2009 and 2018 wasmade. The final sample comprised 14 cases. Results: The average age was 53.5 years; the majority had diagnosis of MM (85.7percent) and all of them were diagnosed in stage III of Durie-Salmon; as CR 64.2 percent received HD-mel, at 200 mg/m2. The recovery of neutrophil and platelet counts occurred on average at 11.4 and 12 days respectively. Transplant related mortality (TRM) at day +30 was 7.1 percent. The probability of OS at 2 years was higher than 90 percent and at 5 years of 68 percent. Conclusions: It was verified that the performance of auto-HSCT with the use of HD-Mel as CR in patients with MG is a feasible procedure in our country with a relatively low TRM. It was possible to demonstrate that the inclusion of auto-HSCT in the treatment considerably improves the survival expectations of these patients(AU)

Hematopoietic stem cell transplantation in children with Griscelli Syndrome type 2: Experience and outcomes

Griscelli syndrome is a rare autosomal recessive inherited disorder characterized by hypopigmentation, silver colored hair, and associated immunological deficiency, which proves fatal in the absence of timely intervention. Our patients diagnosed with Griscelli syndrome-2 presented with fever, hepatosplenomegaly, and deranged hematological and biochemical parameters. Both cases underwent detailed investigations comprising of hair mount microscopic examination, degranulation assay, and mutational studies. Our cases showed defective degranulation activity by NK cells and gene mutation analysis revealed RAB27A mutation that causes defect of cytotoxic granule exocytosis from natural killer (NK) and T-cells, manifesting clinically as hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplantation in one of the patients resulted in stable chimerism; however, the second case relapsed within a month after SCT. Stem cell transplantation is the only curative therapeutic option for GS2; thus, improvement in posttransplantation management may reduce mortality and posttransplant complications. Hence, any child who presents with partial albinism and clinical features suggestive of HLH, a peripheral blood, hair shaft mount examination along with basic immunological NK and T-cell cytotoxicity assay by flow cytometry will help clinch the diagnosis early. It can subsequently be confirmed by molecular study. Timely therapeutic intervention can prevent relapses and severe infection and improve outcome in these cases.

A pilot study on effectiveness of oral mucositis pain control in hematopoietic stem cell transplant patients

Effectiveness of oral mucositis (OM) pain control with the current standard of care management was assessed usingclinician and self-reported scales in hematopoietic stem cell transplant (HSCT) patients. A prospective observationalstudy was performed using clinician-assessed [World Health Organization (WHO)] Oral Toxicity Scales and selfreported scales [Oral Mucositis Daily Questionnaires (OMDQ)]. A total of 23 HSCT patients were included in thestudy. There were 100 recorded days of OM using WHO scores, and 144 recorded days of OM using OMDQ. A totalof 14/23 (60.9%) patients experienced mucositis. The presence of OM was significantly associated with increase inactual body weight [t(21) = 2.15, p = 0.044], body surface area (BSA) [t(21) = 2.31, p = 0.031] and body mass index(BMI) [t(21) = 2.13, p = 0.044], longer hospital stays [t(21) = 2.45, p = 0.023], and busulphan-based regimens (χ = 4.32,p = 0.038). The degree of pain relief was significantly inversely correlated to both the degree of WHO graded OMseverity (ρ = −0.586; p < 0.001) and the severity of self-reported pain (ρ = −0.375; p < 0.001). Both WHO and OMDQsignificantly positively correlated in the clinical setting (p < 0.001). In conclusion, this study highlights the potentialadvantages of using patient self-reported scales in the local clinical setting. The use of the OMDQ self-reported scalescould lead to earlier changes in therapy and may prove useful in HSCT patients.

Assessing the impact of ABO incompatibility on major allogeneic hematopoietic stem cell transplant outcomes: a prospective, single-center, cohort study

Abstract Background ABO blood group incompatibility between donor and recipient is associated with a number of immunohematological complications, but is not considered a major contraindication to allogeneic hematopoietic stem cell transplantation. However, available evidence from the literature seems to be conflicting as to the impact of incompatibility on overall survival, event-free survival, transplant-related mortality, graft-versus-host disease, and time to neutrophil and platelet engraftment. Methods This single-center, prospective, cohort study included patients with hematological malignancies who underwent a first allogeneic hematopoietic stem cell transplantation between 2008 and 2014. Patients receiving umbilical cord blood as the stem cell source were excluded from this analysis. The impact of ABO incompatibility was evaluated in respect to overall survival, event-free survival, transplant-related mortality, acute graft-versus-host disease and engraftment. Results A total of 130 patients were included of whom 78 (60%) were males. The median age at transplant was 36 (range: 2-65) years, 44 (33%) presented ABO incompatibility, 75 (58%) had acute leukemia, 111 (85%) had a related donor, 100 (77%) received peripheral blood hematopoietic stem cells as graft source and 99 (76%) underwent a myeloablative conditioning regimen. There was no statistically significant association between ABO incompatibility and overall survival, event-free survival, transplant-related mortality, grade II-IV acute graft-versus-host disease, neutrophil or platelet engraftment in multivariate analysis. Conclusion These results show that ABO incompatibility does not seem to influence these parameters in patients undergoing allogeneic hematopoietic stem cell transplantation.

A pilot study on effectiveness of oral mucositis pain control in hematopoietic stem cell transplant patients

Effectiveness of oral mucositis (OM) pain control with the current standard of care management was assessed usingclinician and self-reported scales in hematopoietic stem cell transplant (HSCT) patients. A prospective observationalstudy was performed using clinician-assessed [World Health Organization (WHO)] Oral Toxicity Scales and selfreported scales [Oral Mucositis Daily Questionnaires (OMDQ)]. A total of 23 HSCT patients were included in thestudy. There were 100 recorded days of OM using WHO scores, and 144 recorded days of OM using OMDQ. A totalof 14/23 (60.9%) patients experienced mucositis. The presence of OM was significantly associated with increase inactual body weight [t(21) = 2.15, p = 0.044], body surface area (BSA) [t(21) = 2.31, p = 0.031] and body mass index(BMI) [t(21) = 2.13, p = 0.044], longer hospital stays [t(21) = 2.45, p = 0.023], and busulphan-based regimens (χ = 4.32,p = 0.038). The degree of pain relief was significantly inversely correlated to both the degree of WHO graded OMseverity (ρ = −0.586; p < 0.001) and the severity of self-reported pain (ρ = −0.375; p < 0.001). Both WHO and OMDQsignificantly positively correlated in the clinical setting (p < 0.001). In conclusion, this study highlights the potentialadvantages of using patient self-reported scales in the local clinical setting. The use of the OMDQ self-reported scalescould lead to earlier changes in therapy and may prove useful in HSCT patients.

Safety and efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with relapsed/refractory lymphoma

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.

Elementos constitutivos do cuidado às crianças, adolescentes e famílias no transplante de células-tronco hematopoiéticas: percepção da equipe de saúde / Constituent elements of care for children, adolescents and families in hematopoietic stem cell transplantation: perception of the health team

O cuidado corresponde a essência humana e envolve dialogicidade, afeto e inter-relação. O cuidado em saúde extrapola a visão biologicista e higienista, e nega as relações mecanizadas entre o ser que cuida e o ser cuidado. Desse modo, orienta-se pela ética e busca auxiliar o outro nos momentos de fragilidade a fim de que este se restabeleça a partir da sua singularidade. Neste sentido, esta pesquisa objetivou conhecer os elementos constitutivos do cuidado às crianças, adolescentes e famílias no processo de Transplante de Células-Tronco Hematopoéticas (TCTH) alogênico na percepção da equipe de saúde. Trata-se de uma Pesquisa Convergente Assistencial, de abordagem qualitativa. Participaram deste estudo 14 profissionais da saúde que cuidam de crianças e adolescentes durante o TCTH e que respeitavam os critérios de inclusão/exclusão. O cenário desta pesquisa foi a Unidade de Ambiente Protegido ­ Transplante de Medula Óssea de um hospital terciário do sul do país. As informações foram coletadas, nos meses de setembro a dezembro de 2018, por meio de entrevistas semi-estruturadas, as quais foram validadas pelos participantes. Os princípios éticos das pesquisas em ciências humanas e sociais foram respeitados segundo as resoluções nº466 de 2012 e nº510 de 07 de abril de 2016 e a pesquisa foi aprovada pela Comissão de Pesquisa da Escola de Enfermagem da UFRGS e pelo Comitê de Ética em Pesquisa da UFRGS via Plataforma Brasil. A análise das informações foi concomitante às coletas e emergiram três eixos principais intitulados: Construção do cuidado; Melhor interesse da criança e do adolescente; Reflexões dos profissionais sobre o cuidado da criança, adolescente e suas famílias submetidos ao TCTH - composto pelos subeixos: a visão do profissional sobre sua prática de cuidado; enfrentamento do profissional e a visão do profissional sobre o enfrentamento da criança, do adolescente e da família. A partir dos resultados foi possível identificar que o adoecimento da criança e do adolescente representa à família a possibilidade de morte do filho, bem como a perda dos projetos futuros, alterando, assim, sua trajetória de vida sonhada. Essa facticidade existencial soma-se a necessidade de realizar o TCTH, visto que este configura-se como um tratamento associado a altos índices de morbimortalidade. Neste cenário, os profissionais buscam articular seus conhecimentos a fim de estabelecer o melhor plano terapêutico e se sensibilizam diante das situações de vulnerabilidade vivenciadas pelas crianças/adolescentes e famílias. Destaca-se como contribuições para a saúde, em especial para a enfermagem, a visibilidade das percepções sobre o cuidado, evidenciando os aspectos existenciais envolvidos no TCTH. Identifica-se que a subjetividade permeia o processo do cuidado revelando a complexidade de estabelecer os limites terapêuticos e os cuidados paliativos pediátricos, bem como, aceitar a morte da criança e do adolescente como uma facticidade existencial. Esta visão pode ampliar as estratégias de cuidado nessa área.

Care corresponds to a human essence and involves dialogue, affection and interrelation. The health care goes beyond the biological and hygienist view and denies the mechanics relation between who cares and who been cared. It is guided by ethics and seeks to help other in the fragility moments to promove and restored uniqueness. In that way, this research aimed knows the constitutive elements of caring for children, adolescents and families in the process of allogenic hematopoietic stem cell transplant in the perception of health care team. A convergent care research method was adopted with a qualitative approach. Participated of this study a total of 14 health professionals who take care of children, adolescents and families and who respected inclusion/exclusion criteria. The scenario of this research was the Protected Environment Unity ­ TMO in a tertiary referral hospital of south region in Brazil. Informations were collected, during September to November 2018, through semi-structured interviews, which were validated by the participants. Ethical principles in humans and socials sciences research were respected according the resolutions nº 466 of 2012 and nº 510 of April 7th 2016, this survey was approved by the Research Committee of the UFRGS Nursing School and by the CEP of UFRGS via ´Plataforma Brazil´. Analysis information were concomitant with the assessment and showed tree principals axes named: Care construction; Better interest of children and adolescents axis; Professionals reflection about the caring of children, adolescents and their families submitted to HSCT ­ with sub-axes: professional´s perception about their care practice; professional´s coping strategies and their perception about coping strategies of children, adolescents and families. According the results was possible to identify that child and adolescent´s illness represents son´s death possibility for the family, as well as loosing future projects, thus altering their dream life trajectory. This existential facticity there is a need to perform the Hematopoietic Stem Cell Transplant (HSCT), since this is configured as a treatment associated with high rates of morbidity and mortality. In this scenario, professionals can be able to articulate their knowledge to establish the best therapeutic plan and in front of vulnerability situations touch their self by children, adolescents and families experience. As contribution for health, in special for nursing, stands out a visibility for perceptions about care, showing essential aspects involved in HSCT. It was identified that subjectivity permeates the process of care revealing a complexity in the establishment of therapeutic limits and pediatrics palliative care, as well as to accept child and adolescent death as a existential facticity. This vision can broaden strategies care in this area.

A resiliência na trajetória de clientes no pós-transplante de células-tronco hematopoiéticas / La resiliencia en la trayectoria de los clientes en post-trasplante de células madre hematopoyéticas / Resilience in the trajectory client post-transplantation hematopoietic stem cell

RESUMO Introdução: A resiliência apresenta-se como tema relevante de estudo no cotidiano do pós-transplante de células-tronco hematopoiéticas. Objetivo: identificar o nível de resiliência dos clientes no pós-transplante; e analisar os fatores de risco e de proteção, e expectativas presentes no cotidiano do pós-transplante. Metodos: Estudo qualitativo, realizado com 15 clientes no pós-transplante de células-tronco hematopoiéticas da Unidade de Transplante de Medula Óssea de um hospital universitário localizado no município do Rio de Janeiro, Brasil. Os dados foram coletados entre os meses de julho e agosto de 2011, por meio da Escala de Resiliência e da entrevista semiestruturada. Resultados: Os clientes apresentaram uma resiliência moderada, e da análise temática das entrevistas emergiram três subunidades: O tratamento que adoece e que faz perder a potência; Os suportes interno e externo: fortalecendo as estratégias de enfrentamento; e A superação como um processo. Conclusão: Os clientes se encontram em um processo de superação, uma vez que ainda vivenciam as dificuldades decorrentes do tratamento, requerendo estratégias adequadas de enfrentamento. Através dos pressupostos da resiliência, permitiu-se conhecer tais movimentos presentes neste universo, além de fomentar a necessidade de novas pesquisas dentro da temática(AU)

RESUMEN Introducción: La resiliencia presenta un tema relevante del estudio cotidiano post-trasplante de trasplante de células madre hematopoyéticas. Objetivo: Identificar el nivel de resiliencia de los clientes después del trasplante; y analizar el riesgo y los factores protectores presentes en el día a día post-trasplante. Métodos: estudio cualitativo realizado con 15 clientes en el post-trasplante de una unidad de trasplante de médula de un hospital universitario en la ciudad de Río de Janeiro, Brasil. Los datos fueron recolectados entre julio y agosto de 2011, por medio de la Escala de Resiliencia y entrevista semiestructurada. Resultados: Los clientes mostraron una resiliencia moderada, y el análisis temático de las entrevistas revelaron tres subunidades: tratamiento que hace enfermar y hace perder el poder; los soportes interno y externo: el fortalecimiento de las estrategias de supervivencia; y la superación como proceso. Conclusión: Los clientes estaban en un proceso de recuperación, ya que todavía experimentaban las dificultades resultantes del tratamiento, lo que requiere estrategias de afrontamiento adecuadas. A través de los supuestos de la capacidad de recuperación, se le permitió hacer frente a tales movimientos presentes en este universo, así como la promoción de la necesidad de nuevas investigaciones sobre el tema(AU)

ABSTRACT Introduction: Resilience is currently a topic worth studying in daily life for cases of hematopoietic stem cell transplantation. Objective: To identify the level of resilience of the clients after transplant and to analyze the risk and the protective factors present in the day-to-day post-transplant. Methods: Qualitative study conducted on 15 clients in the post-transplant of a bone marrow transplant unit of a university hospital in the city of Rio de Janeiro, Brazil. Data were collected between July and August 2011, through the Resilience Scale and a semi-structured interview. Results: Clients showed moderate resilience, and the thematic analysis of the interviews showed three subunits: treatment that makes people sick and lose power, internal and external supports (strengthening of survival strategies), and overcoming as a process. Conclusion: Clients were in a recovery process, as they still experienced the difficulties resulting from treatment, which requires adequate managing strategies. Through the assumptions of the capacity for recovery, they were allowed dealing with such movements present in this universe, as well as promoting the need for new research on the subject(AU)

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center

ABSTRACT Background: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. Methods: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. Results: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). Conclusions: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Qualidade de vida dos cuidadores principais de pacientes pós-transplante de células-tronco hematopoéticas / Cualidad de vida de los cuidadores principales de pacientes pos-transplante de células-tronco hematopoyéticas / Quality of life of the main caretakers of post-hematopoietic stem-cell transplant patients

RESUMO Objetivo: avaliar e identificar os domínios afetados na qualidade de vida, correlacionar com a sobrecarga de cuidado e o desconforto emocional dos cuidadores principais de pacientes adultos com câncer hematológico submetidos ao transplante de células-tronco hematopoéticas. Método: estudo transversal e retrospectivo realizado com 59 cuidadores principais de pacientes submetidos a esta modalidade de tratamento. Foi caracterizado o perfil sociodemográfico e aplicado o questionário de avaliação de qualidade de vida (Medical Outcomes Study 36 - Item Short Form Health Survey), avaliação do desconforto emocional (Self Reporting Questionnaire) e de sobrecarga de cuidado (Zarit Burden Interview). Resultados: os participantes foram predominantes cuidadores principais do sexo feminino, cônjuges e com nível médio de escolaridade. Na avaliação da qualidade de vida foi observada correlação entre a Capacidade Funcional e Dor e entre Aspectos Emocionais e Saúde Mental. O maior escore apresentado pelo desconforto emocional não foi significativo. Em relação à sobrecarga de cuidado a maior frequência se deu entre sobrecarga moderada e moderada a grave. Conclusão: a qualidade de vida de cuidadores principais destes pacientes é prejudicada em diferentes domínios e a sobrecarga de cuidado é significativa; sugere-se que os cuidadores principais do paciente que realiza o transplante de células-tronco hematopoéticas sejam foco também da equipe multiprofissional que assiste o transplantado visando a promover a melhoria da qualidade de vida de ambos.

RESUMEN Objetivo: evaluar e identificar los dominios afectados en la cualidad de vida, correlacionarla con la sobrecarga del cuidado y el desánimo emocional de los cuidadores principales de pacientes adultos con cáncer hematológico sometidos a un trasplante de células-tronco hematopoyéticas. Método: estudio transversal y retrospectivo realizado con 59 cuidadores principales de pacientes sometidos a esta modalidad de tratamiento. Se caracterizó el perfil sociodemográfico y se aplicó el cuestionario de evaluación de cualidad de vida (Medical Outcomes Study 36 - Item Short Form Health Survey), evaluación del desánimo emocional (Self Reporting Questionnaire) y de la sobrecarga del cuidado (Zarit Burden Interview). Resultados: los participantes fueron, predominantemente, cuidadores principales del sexo femenino, cónyuges y con nivel secundario de escolaridad. En la evaluación de la cualidad de vida se observó la correlación entre la Capacidad Funcional y el Dolor, entre Aspectos Emocionales y de Salud Mental. El mayor resultado presentado por el desánimo emocional no fue significativo. En relación a la sobrecarga del cuidado, la mayor frecuencia se dio entre la sobrecarga moderada y de moderada a grave. Conclusión: la cualidad de vida de los cuidadores principales de estos pacientes es perjudicada en diferentes dominios y la sobrecarga del cuidado es significativa. Se sugiere que los cuidadores principales del paciente que realiza el trasplante de células-tronco hematopoyéticas sean considerados también por el equipo multiprofesional que atiende al trasplantado con el objetivo de promover la mejoría de la cualidad de vida de ambos.

ABSTRACT Objective: to evaluate and to identify the areas affected in the quality of life, to correlate with the care overload and the emotional discomfort of adult patients with hematologic cancer submitted to the hematopoietic stem-cell transplant. Method: cross-sectional and retrospective study carried out with 59 main caretakers of patients submitted to this treatment modality. The sociodemographic profile was characterized and the life quality assessment (Medical Outcomes 36 Study - Item Shorts Form Health Survey), emotional discomfort assessment (Self Reporting Questionnaire) and the care overload (Zarit Burden Interview) questionnaires were applied. Results: the participants were predominantly female, married and with high school education level. In the life quality assessment, the correlation between the Functional Capacity and Pain, and between the Emotional Aspects and Mental Health was observed. The highest score presented by the emotional discomfort was not significant. In relation to the care overload, the greatest frequency was between moderate and moderate to serious overload. Conclusion: the life quality of these patients' main caretakers is harmed in different areas and the care overload is significant; it is suggested that the main caretakers of the patient who undergoes a hematopoietic stem-cell transplant is also the focus of the multiprofessional team that assists the transplanted patient aiming at promoting the quality improvement in both lives.

Establishment of a animal model of allogeneic bone marrow transplantation plus thymic epithelial cells transplantation / 中华器官移植杂志

Objective To explore the establishment of animal model of allogeneic bone marrow transplantation plus thymic epithelial cells transplantation,and then examine the feasibility and effects of thymic epithelial cells transplantation applied in allogeneic bone marrow transplantation.Methods One day before transplantation the recipient BALB/C mice were given total-body irradiation,then transplanted with bone marrow cells from donor C57BL/6 mice and thymic epithelial cells from E14-16 embryonic thymus of donor C57BL/6 mice.In order to explore the appropriate irradiation dose,we set up three different dose groups:7 Gy;6.5 Gy;6 Gy.The recipient mice transplanted with BMT plus TCT served as experimental group,and those transplanted with BMT only served as control group (n =8 each).Then in vivo imaging in mammals was done to observe the thymic epithelial cells transplantation.Thymus index was measured.The thymus in each group was collected for histological examination and immunohistochemical staining of K5 and K8.Flow cytometry was used to examine the T cells subsets in peripheral blood of recipient mice 4 weeks after thymus transplantation.Results The recipient mice with 6.0 Gy TBI had long-term survival but implantation was done unsuccessfully,and those with 6.5 Gy had lower survival rate but implantation was done successfully.6.5 Gy was the minimum lethal dose and could be used as the appropriate irradiation does in this study.In vivo imaging in mammals detecting system showed the experimental group obvious fluorescent signals could be detected in the experimental group,but no fluorescence was found in the control group.Four weeks after transplantation,the thymus was bigger and thymus index was higher in the experimental group than in the control group.And the chiemra thymus of the experimental group also had normal cortex and medulla histological structure.Four weeks after transplantion,the percentages of CD4+ and CD8+ T cells of the peripheral blood in experimental group were significantly higher than in control group (P＜ 0.05).Conclusion Thymic epithelial cells can be transplanted in the thymus of the recipient mice with allogeneic bone marrow transplantation and promote the reconstitution of T lymphocytes of peripheral blood in the recipient mice.

An Analysis of Blood Utilization for Stem Cell Transplant Patients in a Tertiary Care Hospital

BACKGROUND AND OBJECTIVE: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Aga Khan University Hospital. SUBJECTS AND METHODS: A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from June 2014~June 2015. All consecutive patients, admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. RESULTS: During the study period, n=25 patients underwent haematopoietic stem cell transplant. There were n=19 males and n=6 females. One patient was less than 15 years of age while rests were adults. Median age±SD was 26.5±14.5 years (12~54 years). The underlying diagnosis included Aplastic anemia (n=8), Thalassemia major (n=3), Multiple Myeloma (n=4), Acute leukemia (n=5), Hodgkin’s lymphoma (n=4), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204 while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gms/dl. CONCLUSION: The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international benchmark.

Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n = 14) or chronic lymphocytic leukemia (n = 12). The median age was 44 years (range: 24-53 years) and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV) with partial response or stable disease. Most underwent myeloablative conditioning n = 17 - 59%). In this scenario, refractory disease was observed in seven (24%) patients, the 100-day mortality rate was 17% (n = 5) and relapse occurred in four patients (18%). The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.

Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease / Avances recientes en los factores de riesgo, diagnóstico y tratamiento de la enfermedad linfoproliferativa post trasplante con infección por virus de Epstein-Barr

Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.

A cincuenta años de los primeros reportes de asociación del linfoma de Burkitt con el virus de Epstein-Barr (VEB), el VEB ha emergido como el tercer virus de tipo oncogénico con mayor prevalencia a escala mundial. La infección por VEB se asocia con diversas neoplasias, incluyendo el linfoma de Hodgkin y el no Hodgkin, linfoma de células T/NK y carcinoma nasofaríngeo. A pesar del control inmunológico altamente específico en el huésped inmunocompetente, el VEB puede ocasionar complicaciones severas en el huésped inmunocomprometido (es decir, la enfermedad linfoproliferativa post-trasplante). Esto es un problema particularmente en pacientes en quienes se retrasa la reconstitución de la inmunidad después de un trasplante de células madre hematopoyéticas o un trasplante de órganos sólidos. A pesar de los avances en las técnicas de diagnóstico y los algoritmos de tratamiento que permiten la identificación temprana y el tratamiento de pacientes de alto riesgo, las tasas mortalidad siguen siendo muy altas (del 90%) si no se recibe tratamiento temprano. La piedra angular del tratamiento incluye la disminución de la inmunosupresión y la depleción de células B in vivo con un anticuerpo monoclonal anti-CD20. Sin embargo, estas modalidades de tratamiento no son siempre posibles debido al rechazo del injerto, la enfermedad de injerto contra huésped y la toxicidad. Nuevas modalidades de tratamiento incluyen el uso de la terapia adoptiva de células T, que ha mostrado resultados promisorios en diversas neoplasias relacionadas con el VEB. En este artículo se revisan los avances más recientes en cuanto a los factores de riesgo, diagnóstico y tratamiento de las neoplasias asociadas con VEB, particularmente la enfermedad linfoproliferativa post-trasplante. También se discuten los tratamientos más recientes e innovadores, que incluyen la terapia adoptiva de células T así como el manejo de situaciones especiales, como la infección crónica activa de VEB y la linfohistiocitosis hemafagocítica asociada con VEB.