Clinical Study of Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors.@*METHODS@#The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method.@*RESULTS@#Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543).@*CONCLUSION@#Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.

Clinical effect of allogeneic hematopoietic stem cell transplantation in children with hyper-IgM syndrome / 中国当代儿科杂志

OBJECTIVES@#To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM).@*METHODS@#A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT.@*RESULTS@#After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (P=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (P<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (P=0.02) and DFS rate (P=0.04).@*CONCLUSIONS@#Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.

A real life use of ruxolitinib in patients with acute and chronic graft versus host disease refractory to corticosteroid treatment in Latin American patients

Abstract Introduction: Graft-versus-host disease (GVHD) is a serious complication in allogeneic transplantation. The first-line treatment is high doses of corticosteroids. In the absence of response to corticosteroids, several immunosuppressive drugs can be used, but they entail an elevated risk of severe infections. Added to this, there are patients who do not improve on any immunosuppressive treatment, with subsequent deteriorated quality of life and high mortality. Ruxolitinib has been shown to induce responses in refractory patients. In this study we have presented our real-life experience. Methods: A retrospective analysis was performed on patients with severe GVHD refractory to corticosteroids. Demographic, previous treatment, response and mortality data were collected. Results: Since 2014, seventeen patients with GVHD were treated with ruxolitinib due to refractoriness to corticosteroids and immunosuppressants and a few to extracorporeal photopheresis, 8 with acute GVHD (1 pulmonary, 4 cutaneous grade IV and 3 digestive grade IV) and 9 with chronic GHVD (5 cutaneous sclerodermiform, 2 pulmonary and 1 multisystemic). The overall response to ruxolitinib treatment for acute GVHD was 80%, 40% with partial response and 40% with complete remission. Global response in chronic GVHD was 79%. The GVHD mortality was only seen in acute disease and was 40%. Causes of mortality in those patients were severe viral pneumonia, post-transplantation hemophagocytic syndrome and meningeal GVHD refractory to ruxolitinib. Conclusions: In our series, the use of ruxolitinib as a rescue strategy in acute or chronic GVHD was satisfactory. Ruxolitinib treatment in patients with a very poor prognosis showed encouraging results. However, the GVHD mortality remains high in refractory patients, showing that better therapeutic strategies are needed.

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study / 医学前沿

Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P = 0.03 and P = 0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%-86.7%) and 58.4% (95% CI: 41.9%-81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%-35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%-38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included. Forty-five (79%) patients had a malignant disease. Alemtuzumab was administered before the conditioning regimen at a dose of 1 mg/kg in children and 30 mg/day for 2 days in adults or children weighing more than 40 kg (a total dose of 60 mg) with a non-malignant disease or patients with a malignant disease and high-risk for GVHD mortality. Alemtuzumab was used in 23 (40%) patients, of whom 17 received a reduced-intensity conditioning. Eleven patients presented aGVHD (grade 2–4) and only 1 of them received alemtuzumab. Cumulative incidence of aGVHD (grade 2–4) at day 100 after transplantation (D+100) was 4 for patients receiving alemtuzumab and 29% for patients not receiving alemtuzumab. Cumulative incidence of cytomegalovirus reactivation for patients receiving or not alemtuzumab was 62 and 38%, respectively. Sixteen patients died in the first 100 days after alloHSCT, most of them due to bacterial sepsis. Only 2 patients died of aGVHD until D+100. Overall survival was 50% without any impact of alemtuzumab. Alemtuzumab effectively controlled aGVHD but increased the risk of cytomegalovirus reactivation without improving survival.

Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic.

Allogeneic hematopoietic stem cell transplantation in the elderly: Predicting the risk for non relapse mortality

We have retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplantation (HSCT) between January 1997 and July 2013. Median follow up was 1.3 years. Sex, age, diagnosis, disease stage, comorbidities (according to HCT-CI score), type of donor, histocompatibility, conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were evaluated. The incidence and severity of acute and chronic GVHD, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse were investigated according those variables. Acute GVHD incidence was 41% (7.3% GIII-IV). Patients with acute myeloid leukemia had lesser aGVH GII-IV (14% vs. 35%, p < 0.01) comparing to the entire population. Extensive cGVHD incidence was 9.4%. Global OS 1-3 years was 44-20%, DFS 33-20%, relapse 35-41% and NRM 36-43% respectively. The presence of comorbidities showed a significant increase in NRM (CT-CI 0 vs. 1 vs ≥ 2: 1-3 years 17-24% vs. 40-46% vs. 45-67%, p = 0.001, MA HR 2.03, CI 95% 1.02-5.29), as well as cyclosporine vs. tacrolimus (1-3 years 47-53% vs. 25-36%, p = 0.01). Tacrolimus patients had higher 1-3 years OS (49-25% vs. 31-13%, p = 0.01) and DFS (41-26% vs. 20-11%, p < 0.01). Age, type of donor and myeloablative conditioning showed no significant differences in any outcome. Allogeneic HSCT is a valid therapeutic option for older patients in Argentina. The main risk factor for a significantly increased NRM and a trend to inferior OS was the number of comorbidities. Age was not a factor for a worse result. The other factor having a significant effect in better outcome was tacrolimus administration.

Se efectuó un análisis retrospectivo de 137 historias clínicas de pacientes mayores de 50 años que recibieron un trasplante alogénico de precursores hematopoyéticos (TAPH). Se evaluaron las siguientes características: sexo, edad, enfermedad, estadio, comorbilidades (según el HCT-CI), donante, acondicionamiento e inmunosupresión. Se analizó la incidencia de enfermedad injerto vs. huésped aguda (aEICH) y crónica (cEICH), supervivencia global (SG), supervivencia libre de enfermedad (SLE), recaída y mortalidad libre de enfermedad (MLE). Los trasplantes fueron realizados entre 1997-2013, mediana de seguimiento 1.3 años. La incidencia de aEICH fue de 41% (7.3% GIII-IV). Los pacientes con leucemia mieloide aguda presentaron menor incidencia de EICHa GII-IV (14% vs. 34%, p < 0.01). La incidencia de EICHc extenso fue de 9.4%. La SG a 1-3 años fue 44-20%, SLE 33-20%, recaída 35-41% y la MLE 36-43%. Los pacientes con comorbilidades tuvieron un aumento significativo de la MLE (HCT-CI 0 vs. 1 vs. ≥2: 1-3 años 17-24% vs. 40-46% vs. 45-67%, p = 0.001, AMV HR 2.03, IC 95% 1.02-5.29), al igual que el uso de ciclosporina vs. tacrolimus (1-3 años 47-53% vs. 25-36%, p = 0.01). Los pacientes que recibieron tacrolimus tuvieron una mayor SG (1-3 años 49-25% vs. 31-13%, p = 0.01) y SLE (1-3 años 41-26% vs. 20-11%, p < 0.01). La edad, tipo de donante y acondicionamiento no resultaron significativos para ningún evento. El TAPH es una herramienta terapéutica válida en pacientes mayores. Los factores pronósticos que inciden mayormente en el trasplante son las comorbilidades y no la edad. El otro factor que demostró un efecto significativo fue el uso de tacrolimus.

CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations

BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.

Enfermedad injerto versus huésped / Graft versus host disease

La enfermedad injerto versus huésped (EIVH) es una entidad de frecuente presentación en las personas que son intervenidas con alotrasplantes. Es inducida y mantenida por las células inmunocompetentes del injerto, que atacan los tejidos del huésped; especialmente los epitelios. El diagnóstico de la EIVH es clínico, apoyado en la histopatología, pero esta, por sí misma, no permite diagnosticar la entidad. La primera línea de tratamiento de la EIVH continúan siendo los esteroides sistémicos y ante refractariedad para estos, aparecen nuevas terapéuticas que resultan efectivas en casos reportados en la literatura, sin que aún se hayan podido definir guías de manejo para este tipo de pacientes. Se necesita realizar estudios de terapéutica en pacientes refractarios a esteroides para poder concluir al respecto.

Graft versus host disease is a condition of frequent occurrence in people who are implanted with allogeneic transplants. The diagnosis is clinical, supported by histopathology, but this, by itself does not make a diagnosis. The first line of treatment for this entity are systemic steroids. For the patient refractory to systemic steroids, new therapeutics that could be useful are reported, but not yet defined its use and none were superior to steroids. Studies are needed to define the approach to the patient refractory to steroids.

Prevalence of chimerism after non-myeloablative hematopoietic stem cell transplantation / Prevalência do quimerismo após transplante de células hematopoiéticas não-mieloablativo

Context and objective: Non-myeloablative hematopoietic stem cell transplantation (NMA-HSCT) is performed in onco-hematological patients who cannot tolerate ablative conditioning because of older age or comorbidities. This approach does not completely eliminate host cells and initially results in mixed chimerism. Long-term persistence of mixed chimerism results in graft rejection and relapse. Involvement of graft-versus-host disease is concomitant with complete chimerism and graft-versus-tumor effect. The aim of this study was to evaluate the prevalence of chimerism in onco-hematological patients who underwent NMA-HSCT. Desingn and setting: Observational clinical study on chimerism status after human leukocyte antigen-identical NMA-HSCT at the Discipline of Hematology and Hemotherapy of Universidade Federal de São Paulo. Methods: We sequentially analyzed the amplification of APO-B, D1S80, DxS52, FVW, 33.6, YNZ-2 and H-ras primers using variable number of tandem repeats (VNTR) on 17 pairs and fluorescent in situ hybridization (FISH) with the XY probe and SRY primer on 13 sex-unmatched pairs. RESULTS: The informativeness of the primers using VNTR was 60 percent for APO-B, 75 percent D1S80, 36 percent DxS52, 14 percent FVW, 40 percent YNZ-22 and 16 percent H-ras. The SRY primer was informative in female receptors with male donors. The XY-FISH method was informative in 100 percent of the sex-unmatched pairs. Conclusion: These methods were sensitive and informative. In VNTR, the association of APO-B with D1S80 showed 88 percent informativeness. The quantitative FISH method was more sensitive, but had the disadvantage of only being used for sex-unmatched pairs.

Contexto e objetivo: O transplante de células hematopoiéticas não-mieloablativo é realizado em pacientes com doenças onco-hematológicas que não suportam condicionamentos ablativos devido à elevada idade ou ao acometimento por comorbidades. Esta abordagem não elimina completamente as células do hospedeiro, resultando, inicialmente, em quimerismo misto. A persistência do quimerismo misto na evolução de longo prazo resulta na rejeição ao enxerto e recaída. O acometimento pela doença do enxerto contra hospedeiro é concomitante ao quimerismo completo e ao efeito enxerto versus tumor. O objetivo deste estudo foi avaliar a prevalência do quimerismo em doenças onco-hematológicas tratadas com o transplante não-mieloablativo de células hematopoiéticas. Tipo de estudo e local: Estudo clínico observacional do estado de quimerismo após transplante antígenos leucocitários humanos-idêntico não-mieloabaltivo realizado na Disciplina de Hematologia e Hemoterapia da Universidade Federal de São Paulo. Métodos: Analisamos sequencialmente a amplificação dos primers APO-B, D1S80, DxS52, FVW, 33,6, YNZ-22, H-ras pelo VNTR (variable number of tandem repeats) em 17 pares e FISH (fluorescent in situ hybridization) pela sonda XY e do primer SRY em 13 pares de não relacionados a sexo. Resultado: A informatividade dos primers pelo VNTR foi de 60 por cento para APO-B; 75 por cento D1S80; 36 por cento DxS52; 14 por cento FVW; 40 por cento YNZ-22 e 16 por cento H-ras. O primer SRY foi informativo em receptores femininos com doadores masculinos. O método XY-FISH foi informativo em 100 por cento dos pares de não relacionado a sexo. Conclusão: Estes métodos foram sensíveis e informativos. No VNTR, a associação do APO-B com D1S80 mostrou 88 por cento de informatividade. O FISH, método quantitativo, foi mais sensível, porém com desvantagem de ser usado somente nos pares não relacionados a sexo.

Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation

BACKGROUND/AIMS: The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. METHODS: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. RESULTS: When the same dose of T cells, 5-10x10(5) (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graft-versus-host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. CONCLUSIONS: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.

Results of hematopoietic cell transplantation in pediatric leukemia

Hematopoietic cell transplantation [HCT] is an accepted treatment for acute myeloid leukemia [AML] in first remission, the treatment of choice for chronic myeloid leukemia [CML] and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings [57.6%] and autologous transplantation [42.4%]. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 +/- 4.7 X 10[8] /Kg [body weight of patients] and mononuclear cells were 5.5 +/- 2.9 X 10[8]/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin +/- methotrexate. GVHD occurred in 50 [54.3%] patients. Eighty five of children had engraftment, 26 [28.6%] relapsed and 57 [62%] are alive. The most common cause of death was relapse [68.6%]. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time [P = 0.06]. Longer survival significantly related to earlier WBC and platelet recovery [P < 0.0001 and P = 0.006 respectively]. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children

A espirometria na avaliação pré e pós-transplante de medula óssea / Pre-operative and post-operative spirometry in bone marrow transplant patients

OBJETIVO: Analisar os resultados da espirometria de pacientes submetidos a transplante de medula óssea e verificar sua importância na detecção de complicações pulmonares e sua correlação com a evolução dos pacientes. MÉTODOS:Foram analisados retrospectivamente os resultados da espirometria em 120 pacientes, maiores de doze anos, de ambos os sexos, e comparados com o tipo de transplante de medula óssea, doença de base, sorologia para citomegalovírus, fonte de células para o transplante, tabagismo, infecção pulmonar, doença pulmonar prévia, duração da doença hematológica, quimioterapia utilizada, regime de condicionamento, doença do enxerto contra o hospedeiro aguda e crônica e óbito. RESULTADOS: Dezesseis pacientes apresentaram alterações da espirometria antes do transplante, sendo 5 por cento com obstrução pura, 5,8 por cento com restrição pura e 2,5 por cento com obstrução com redução da capacidade vital. Após o transplante 29 pacientes apresentaram alterações desses exames. A chance de alteração da espirometria foi maior nos pacientes com doença do enxerto contra o hospedeiro aguda (p = 0,02), idade menor que 30 anos (p = 0,02), sexo feminino (p = 0,02) e naqueles que receberam células tronco (p = 0,01). As presenças de doença pulmonar prévia e doença do enxerto contra o hospedeiro crônica associaram-se com aumento da mortalidade. Alterações prévias da espirometria não estiveram relacionadas com o óbito pós-transplante. CONCLUSÃO: As alterações detectadas na espirometria não foram capazes de predizer a ocorrência de complicações pulmonares e óbito pós-transplantes. Também não foram determinantes para a não realização do procedimento. A espirometria simples realizada na avaliação desses pacientes parece ter pouca importância prática.

OBJECTIVE: To analyze the spirometry findings in patients undergoing bone marrow transplant, determining the importance of such findings in predicting postoperative pulmonary complications and looking for correlations with postoperative outcomes. METHODS:The spirometry findings in 120 male and female patients, all above the age of 12, were evaluated retrospectively and compared in terms of the following parameters: the type of bone marrow transplant; the underlying disease; cytomegalovirus serology; source of the transplanted cells; smoking; pulmonary infection; history of lung disease; duration of the hematological disease; chemotherapy employed; conditioning regimen; acute or chronic rejection of the transplant; and post-operative mortality. RESULTS: In the pre-operative spirometry, 16 patients (13.3 percent) presented alterations: 6 (5 percent) presented pure obstruction; 7 (5.8 percent) presented pure restriction; and 3 (2.5 percent) presented obstruction accompanied by a reduction in vital capacity. In the post-operative spirometry, 29 patients (24.2 percent) presented alterations. The chance of presenting post-operative spirometry alterations was greater in patients presenting acute transplant rejection (p = 0.02), patients older than 30 (p = 0.02), female patients (p = 0.02) and patients receiving stem cells (p = 0.01). Having a history of lung disease was found to be associated with greater mortality, as was suffering from chronic transplant rejection. No relationship was found between pre-operative spirometry alterations and post-operative mortality. CONCLUSION: In bone marrow transplant patients, the alterations found through pre-operative spirometry were not predictive of post-operative pulmonary complications or mortality. Nor were such alterations determinant of whether or not a given patient was a good candidate for bone marrow transplant. Simple spirometry seems to be of little practical importance in the evaluation of such patients.

Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution

We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51 percent) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23 percent of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38 percent at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.

Allogeneic peripheral blood hematopoietic stem cell transplantation for patients with hematologic malignancies / 华中科技大学学报（医学）（英德文版）

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT). 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft-versus host disease (aGVHD) was prevented by cyclosporin A and short-term MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 x 10(8)/kg and that of the CD34+ cells was 7.8 x 10(6)/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got II degrees-IV degrees aGVHI) and the incidence was 17.5%. Fourteen patients got cGVHD and the incidence was 53.8% in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5% and 2 patients relapsed (5.0%). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor

GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially expressed on CD4+CD25+ regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in chronic graft-versus-host disease (cGVHD), a lupus-like autoimmune disease. A single injection of anti-GITR monoclonal antibody (DTA-1) was effective in blocking the progression of cGVHD in the parent-into-F1 model. Treatment of DTA-1 significantly decreased levels of IgG1 anti-DNA autoantibody, inhibited glomerulonephritis, and increased survival. The DTA-1-mediated inhibition of autoantibody production correlated with deletion of B cells and could occur independently of CD4+CD25+ regulatory T cells. Our results indicate that anti-GITR monoclonal antibody may be used as a potential immunotherapeutic agent for preventing cGVHD.

Doença do Enxerto-Contra-Hospedeiro (DECH) em pacientes transplantados de medula óssea: relato de caso / Graft-Versus-Host-Disease in patientes submitted to bone marrow transplantation: case report

Doença do Enxerto-Contra-Hospedeiro (DECH), é a maior causa de morbidade em pacientes submetidos à transplante de medula óssea. Os autores apresentam dois casos de DECH crônica e descrevem os cuidados com as complicações orais. Esse estudo sugere que, para a redução da morbidade, a avaliação estomatológica e o tratamento de todas as fontes de infecção bucal em potencial, devem se tornar padrão de cuidados para esses pacientes.

Trasplante no mieloablativo de células progenitoras hematopoyéticas: Mitos y realidades / Non-myeloablative transplant of hematopoyetic precursor cells: Myth and reality

The feasibility of applying allogeneic cell -mediated therapy in conjunction with allogeneic hematopoietic cell transplantation following reduced -intensity conditioning, with minimal toxicity and no serious transplant-related complications, makes it possible to perform such procedures on an outpatient basis as well to offer a valid option for cure to elderly individuals and patients with less than optimal performance status. Based on available experience, clinical application of this innovative therapy may open new horizons for the treatment of patients with leukemia, lymphoma, myeloma and other diseases. Many patients can now benefit from the advantages of immunotherapy mediated by alloreactive donor lymphocytes, while minimizing transplant-related toxicity and mortality. This kind of transplant is making real progress in the world of transplantation.

El trasplante alogénico no mieloablativo basa su efecto en la capacidad de los linfocitos del donador de erradicar a la enfermedad residual del paciente. El empleo de dosis reducidas de intensidad de radioterapia y/o quimioterapia permite su empleo en pacientes de edad avanzada y aún con comorbilidad. La poca toxicidad del procedimiento evita frecuentemente la hospitalización del paciente, se asocia a menor frecuencia de infecciones y de transfusiones, por ello el costo es sensiblemente menor e ideal para países pobres. Se ha utilizado con éxito desde hace ocho años y en nuestro país su aplicación es cada vez más frecuente. La utilidad principal se ha observado en leucemias crónicas y linfomas indolentes. En leucemia aguda mieloblástica en primera remisión también es útil, siendo menos efectivo en la leucemia aguda linfoblástica y los linfomas no-Hodgkin agresivos. También puede ser utilizado en niños y en pacientes con enfermedades benignas. El trasplante no-mieloablativo es una realidad en el área de los trasplantes.

Allogeneic peripheral blood stem cell transplant [PBSCT] using anti-IL2 receptor antibody daclizumab for the prevention of acute graft versus host disease in steroid refractory diamond blackfan anaemia: a case report

The case report of a 2 year old boy with steroid refractory DBA, treated with allogeneic PBSCT from an HLA matched sibling is presented. Anti-IL2 receptor antibody Daclizumab was used as a prophylaxis for graft versus host disease [GvHD]. Complete recovery without any evidence of GvHD ensued