Long-term outcome and prognostic factors of unrelated cord blood transplantation in children with haematological malignancies: a retrospective study using the Spanish Working Party for BMT in Children (GETMON) database.

Outcomes of unrelated cord blood transplants (UCBT) were assessed in 172 consecutive children, median age 5 years (range: 0.5-18), with haematological malignancies treated at nine Spanish hospitals between February 1996 and April 2009. Data were collected from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) database. ALL was diagnosed in 125 patients, AML in 43 and myelodysplastic syndrome in 4. Myeloid engraftment (ANC⩾0.5 × 10(9)/L) occurred in 87.2% at a median of 22 days and was associated with the total nucleated cell (TNC) dose infused and use of a TT-containing conditioning regimen. Cumulative incidence of relapse was 20% at 1 year post transplant and 29% at 3 years, being higher in patients with a diagnosis of ALL, very high risk disease and GVHD grades 0-1. Cumulative incidence of non-relapse mortality (NRM) was 19% at 100 days post transplant and 39% at 1 year. BU-FLU-TT-ATG-conditioned patients had lower NRM. Disease-free survival (DFS) was 40% at 2 years post transplant (for patients transplanted since 2006). On multivariate analysis, TNC dose infused, AML and BU-FLU-TT-ATG-conditioning regimen increased the probability of DFS. It is of paramount importance to select cord blood units with the highest cell dose. As the BU-FLU-TT-ATG-conditioning regimen was associated with better DFS owing to lower NRM, further prospective studies testing this regimen are warranted.

Allogeneic hemopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission-similar outcomes after matched related and unrelated donor transplant: a study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon).

The authors report the results of 58 children with ALL in 2CR after related (n = 31) or unrelated (n = 27) AHSCT. Characteristics at diagnosis and initial and after relapse antileukemic treatment were similar in the related donor (RD) and the unrelated donor (UD) groups. Conditioning consisted of TBI/CY +/- VP-16 for patients > or = 3 years old (n = 43) and Bu/CY for the rest. Median recipient age was 8 years (range 1-17) in the RD and 9 years (range 3-14) in the UD group. Median follow-up was 54 months (range 24-80) and 52 months (range 22-85) in the RD and the UD groups repectively. The 5-year EFS probability was 43 +/- 9% for the RD group and 36 +/- 9% in the UD group (p = .25). The transplant-related mortality was 16% in the RD and 37% in the UD group (p = .016). In the RD group 36.7% of patients relapsed versus 18.6% in the UD group (p = .05). GvHD associated with organ failure or infection caused most of the transplant-related deaths in both groups. Survivor quality of life for both groups was good (Lansky score < or = 90).

Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON).

Allogeneic stem cell transplantation is the only curative treatment for Wiskott-Aldrich syndrome. The authors retrospectively analyzed the outcome with this procedure in 13 patients with severe Wiskott-Aldrich syndrome transplanted in 5 Spanish centers from 1989 to 2006. A patient was transplanted twice from the same donor due to a late engraftment failure. Age at transplant ranged from 7 to 192 months (median 30 months). There were 10 matched donors (3 related and 7 unrelated), 2 mismatched unrelated, and 1 haploidentical. Conditioning regimen consisted of busulfan and cyclophosphamide (BuCy) in 11 cases and fludarabine and melfalan (1) or BuCy (1). ATG was added in transplants from non-genetically matched donors. GvHD prophylaxis consisted of cyclosporine and methotrexate in most patients plus T-cell depletion in the haploidentical HSCT. Nine of the 13 transplanted patients are alive with complete clinical, immunologic, and hematologic recovery 8-204 months (median 101 months) after HSCT. Eight surviving patients had been transplanted from matched donors (3 related and 5 unrelated) and 1 from a haploidentical donor. Four patients died, 2 transplanted from matched donors (1 from acute GvHD and organ failure, 1 from a lymphoproliferative disorder after a second transplant), and 2 transplanted from mismatched unrelated donors (1 from acute GvHD and organ failure, 1 from graft failure and infection). Allogeneic hemopoietic stem cell transplantation must be utilized in all patients with severe Wisckott-Aldrich syndrome, using the most suitable graft variant for each patient.

Reconstitución autóloga no leucémica tras un trasplante de progenitores hematopoyéticos en un paciente con leucemia mieloide crónica Ph positivo / Non-leukemic autologus reconstition alter hematopoietic stem cell transplantation in a patient with Ph positive chronic mieloide leukemia

Se presenta el caso de un paciente de leucemia mieloide crónica Ph + sometido a trasplante alogénico de células de cordón umbilical de donante no emparentado. El enfermo presentó reconstitución medular antóloga pero en situación de remisión hematológica y citogenética en la que continúa más de 7 años después del trasplante: se revisa la literatura disponible y se comentan las hipótesis actualmente debatidas para explicar estas situaciones (AU)

The case of a patient with Ph + chronic myeloid leukemia subjected to allogenic transplantation of umbilical cord cells form unrelated donor is presented. The patient had antologous bone marrow reconstitution but in situation of hematological and cytogenetic remission in which he continued for more that 7 years after the transplant. The available literature is reviewed and the presently debated hypotheses to explain these situations are commented on (AU)

Adenitis cervical por Micobacterium scrofulaceum / No disponible

La incidencia de adenitis cervical por micobacterias atípicas ha aumentado en los últimos años, especialmente por el complejo Micobacterium avium-intracellulare y Micobacterium scrofulaceum. Presentamos dos casos clínicos de dos niñas con adenopatía submandibular unilateral de más de 2 semanas de evolución. En ambos casos se inició un ciclo antibiótico con amoxicilina-ácido clavulánico sin objetivarse mejoría. En su evolución ambas pacientes desarrollaron una adenitis cervical supurada. El hemograma, las serología y la radiografía de tórax, no aportaron datos de interés. El Mantoux fue positivo; de 8 y 12 mm, respectivamente. En el estudio microbiológico de las adenitis se obtuvo tinción de ziehl-auramina positiva y en el cultivo de micobacterias crecieron colonias de Micobacterium scrofulaceum. Ambos casos recidivaron tras una cirugía parcial inicial. Finalmente se trataron mediante extirpación quirúrgica de todos los ganglios afectados, añadiendo en una de las pacientes tratamiento antibiótico (AU)

The incidence of cervical adenitis caused by atypical mycobacteria has increased in recent years, especially due to the Mycobacterium avium-intracellulare complex and Mycobacterium scrofulaceum. We present two clinical cases of two female children with unilateral submandibular adenopathy having more than 2 week´s evolution. In both cases, an antibiotic cycle was initiate with amoxicillin-clavulanic acid without observing improvement. In their course, both patients developed supurative cervical adenitis. The complete blood count, serologies and chest X-ray did not provide any data of interest. Mantoux was positive: from 8 and 12 mm respectively. Zichl-auramine staining was positive in the microbiologic study of adenitis and Mycobacterium scrofulaceum colonies grew in mycobacteria culture. Both cases reoccurred after initial partial surgery. Finally, they were treated with surgical excision of all the lymph nodes involved, adding antibiotic medical treatment in one of the patients (AU)

Púrpura trombopénica inmunológica en la infancia / Immunological thromhopenic purpura in childhood

La púrpura trombopénica idiomática es una enfermedad común en la edad pediátrica con tendencia a resolverse espontáneamente en la mayor parte de los casos. Sin embargo, en cerca de un 15% evoluciona a formas crónicas rebeldes a todo tratamiento que afectan significativamente a la calidad de vida de los pacientes y de sus familias. La falta de evidencia en la literatura actual hace que su manejo se base a menudo en la opinión y las prácticas locales. Presentamos 5 casos que ejemplifican los diferentes cursos clínicos y respuestas al tratamiento, así como una puesta al día de lo publicado hasta la fecha (AU)

Idiopathic thrombopenic purpura is a common disease in the pediatric with tendency to resolves spontaneously in most of the cases. However, it evolves to chronic forms resistant to all treatmentsin approximately 15%. These significantly affect the quality of life of the patients and their families. Because of lack of evidence in the present literature, its management is often based on opinion and local practices. We present 5 cases thet illustrate the different clinical courses and responses to treatment and an up-dating of that published up to now (AU)

Prevención y tratamiento de las infecciones en el paciente oncológico pediátrico / Prevention and treatment of infections in pediatric oncology patient

No disponible

No disponible

Supervivencia libre de enfermedad y función renal normal a los 10 años post diagnóstico en tumor de Wilms bilateral / Disease free survival and normal renal function at 10 years post-diagnosis in bilateral Wilms´ tumor

La afectación bilateral representa alrededor del 6 por ciento de los pacientes con tumor de Wilms. Ésta plantea un verdadero reto para el equipo terapéutico: conseguir la curación y evitar recidivas preservando una función renal aceptable, evitando así la anuria que obligaría a un trasplante. Presentamos el caso de una niña diagnosticada a los 22 meses de tumor de Wilms bilateral que tras quimioterapia, cirugía y radioterapia se encuentra libre de enfermedad y con función renal normal a los 10 años post diagnóstico (AU)

Segundo trasplante de precursores hematopoyéticos en un paciente con leucemia mieloide crónica / Second hematopoietic precursor transplant in a patient with chronic myeloid leukemia

El único tratamiento curativo bien documentado para la leucemia mieloide crónica en la infancia es el trasplante de precursores hematopoyéticos alogénico. Para los pacientes que recaen, una buena opción terapéutica es un segundo trasplante. Se debe considerar en aquellos casos que recaen tras más de 12 meses postrasplante evitando regímenes de acondicionamiento excesivos. Presentamos un caso de un paciente que recibió un segundo trasplante de precursores hematopoyéticos alogénico ante una recaída tardía de su enfermedad, consiguiéndose una remisión clínica y citogenética mantenida tras 7,5 años del mismo (AU)

Síndrome de compresión medular aguda en el sarcoma de Ewing / Acute spinal cord compression syndrome in Ewing's sarcoma

La compresión medular es una complicación poco frecuente en la patología tumoral infantil. Puede ser la forma de presentación del proceso neoplásico o bien aparecer a lo largo de la evolución del mismo. La neoplasia que con mayor frecuencia desarrolla esta complicación es el sarcoma de Ewing. Presentamos los casos clínicos de tres niñas con compresión medular aguda por sarcoma de Ewing. El primero de ellos es una niña de 14 años que, tras referir dolor de espalda durante 1 mes, ingresa con cuadro de paraplejía súbita. En la radiografía se evidenciaba afectación de D7. Tras recibir tratamiento quirúrgico de urgencia, fue diagnosticada de sarcoma de Ewing y se efectuó tratamiento para dicha enfermedad. Actualmente, transcurridos 16 años del diagnóstico, la paciente se encuentra en remisión completa y con paraplejía de miembros inferiores. El segundo caso es el de una niña de 13 años que tras lumbalgia durante 4 meses ingresa por pérdida de fuerza en miembros inferiores con conservación de la deambulación. La resonancia magnética mostraba afectación de L2L3. Tras cirugía de urgencia y diagnóstico anatomopatológico, se aplicó tratamiento para su enfermedad tumoral, transcurridos 16 años la paciente se encuentra en remisión completa y con funcionalidad plena de miembros inferiores. Por último, presentamos el caso de una niña de 14 años que durante el estudio de masa pélvica tiene un cuadro de paraplejía súbita de miembros inferiores. Se encontró afectación en múltiples niveles medulares en la resonancia magnética así como metástasis pulmonares y en otros huesos. Actualmente la paciente se encuentra en tratamiento para sarcoma de Ewing y con paraplejía de miembros inferiores. En resumen, ante un cuadro de dolor de espalda prolongado es necesario descartar la etiología tumoral y valorar, mediante adecuada exploración neurológica y prueba de imagen, el riesgo de compresión medular aguda (AU)

El tratamiento de la linfohistiocitosis hemofagocítica familiar. A próposito de una observación / No disponible

La linfohistiocitosis hemafagocítica familiar (LHF) es una enfermedad caracterizada por proliferación y activación de histiocitos y linfocitos T que se acumulan en múltiples órganos con fenómenos de hemofagocitosis. Los criterios diagnósticos incluyen fiebre, esplenomegalia, citopenias, hipertrigliceridemia, hipofibrinogenemia e histología con hemofagocitosis a múltiples niveles. Se describe el caso de una niña de 8 años, con hermana menor fallecida a los 2 años por cuadro de esplenomegalia y pancitopenia. La paciente presentó una LHF tratada tardíamente que evolucionó con afectación del sistema nervioso central durante el período de búsqueda de un donante de progenitores hematopoyéticos histocompatible no emparentado. La enferma falleció el día +5 postrasplante por hemorragia cerebral (AU)

Familial hemophagocytic lymphohistiocytosis (FHL) is a disease characterized by proliferation and activation of histocytes and lymphocytes T that accumulate in multiple organs with hemophagocityosis phenomena. The diagnosis criteria include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia and histology, with hemophagocityosis on multiple levels. A case is described of and 8 year old girl, whose younger sister died at 2 years due to a picture of FHL treated late that evolved with involvement of the Central Nervous System while searching for a histocompatible unrelated hematopoietic stem cell donor. The patient died on day 5 after the transplantation due to brain hemorrhaging (AU)

Matched-pair analysis comparing allogeneic PBPCT and BMT from HLA-identical relatives in childhood acute lymphoblastic leukemia.

This multicenter study was designed to evaluate whether allo-PBPCT provides some advantages, if any, over BMT in terms of engraftment kinetics, acute and chronic GVHD incidence, TRM, relapse incidence and survival in acute lymphoblastic leukemia patients (ALL). From January 1995 to December 1999, 67 ALL patients (34 in the PBPCT group and 33 in the BMT group) were included in this study. Median age for both groups was 8 years (range, 1-18). There were 24 patients in first or second CR in the PBPCT group and 28 such patients in the BMT group. Preparatory regimens were TBI-based in 26/34 in the PBPC group and 25/33 in the BMT group. GVHD prophylaxis was CsA alone in 38 patients (18 PBPCT vs 20 BMT) and CsA plus short Mtx in 29 (16 PBPCT vs 13 BMT). Engraftment was achieved in all cases. Median days to neutrophil recovery was 10 (range, 7-18) after PBPCT vs 14 (range, 9-21) after BMT (P < 0.0001). Platelet engraftment (>50 x 10(9)/l) was also faster for PBPCT patients (median 13 days, range, 9-40 vs 23 days, range, 15-165) (P < 0.0001). Acute GVHD grade II-IV incidence was similar in both groups (46.4 +/- 8.8% vs 42.7 +/- 8.6%) (P = 0.45). Probability of chronic GVHD was 50.6 +/- 12.2% after PBPCT vs 27.8 +/- 9.2% after BMT (P = 0.1). Probability of relapse was similar (28.7 +/- 9.2% for PBPCT vs 27.1 +/- 8.2% for BMT) (P = 0.89). There were eight patients who died from transplant-related complications after PBPCT vs 5 after BMT (P, NS). With a median follow-up of 25 months the event-free survival probability was 53 +/- 8.9% for PBPCT vs 54.9 +/- 9.7% for BMT (P = 0.54). Using PBPC for allogeneic transplantation in childhood ALL results in faster hematopoietic recovery compared to BM, with a similar incidence of aGVHD, TRM, relapse and disease-free survival. However, the issue of cGVHD remains unresolved.

Síndrome de Hermansky-Pudlak / Hermansky-Pudlak syndrome

Se describe un caso de síndrome de Hermansky-Pudlak (SHP) en un enfermo con albinismo conocido y que fue descubierto por sangrado intenso postamigdalectomía. En los estudios de hemostasia realizados se comprobó la existencia de enfermedad de von Willebrand tipo I junto con alteraciones de la agregación plaquetaria. El paciente tuvo que ser intervenido por colelitiasis con colecistectomía, para la cual se administró profilaxis con desmopresina, sin que aparecieran sangrados patológicos ni otras complicaciones (AU)

High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support. Groupo Español de Trasplante de Médula Osea en Niños.

PURPOSE: Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS: We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS: With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION: SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.

[Reconstitution of peripheral blood lymphocytes in patients treated with bone marrow transplantation: comparison between allogeneic and autologous transplantation]. / Reconstitución de los linfocitos de sangre periférica en pacientes tratados con trasplante de médula ósea: comparación entre el trasplante alogénico y el autólogo.

BACKGROUND: This study compares the immune reconstitution of total T cells, CD4 and CD8 cell subsets, activated T cells, NK cells and B cells in 66 patients who underwent allogeneic or autologous bone marrow transplantation (BMT). PATIENTS, MATERIAL AND METHODS: The reconstitution of peripheral lymphocytes subsets was studied using two-color flow cytometry. The study group consisted of 39 patients who received allogeneic BMT compared with 27 patients who received autologous BMT. Peripheral blood was examined at different time intervals. As a measure of immune function, the response to the mitogen phytohemaglutinin (PHA) was determined. RESULTS: The pattern of recovery of CD3+, CD4+ and CD8+ T cells, as well as the PHA response, was similar for each type of transplant. CD3+CD5- cells were significantly higher following autologous BMT than after allogeneic BMT and during more time. An overexpression of DR on T cells following autologous or allogeneic BMT demonstrates an increasing degree of T-lymphocyte activation. This activated T-cell subset was more stable in patients transplanted with allogeneic BM than in patients treated with autologous BM. The levels of total B cells and CD19+CD5+ B-cells were increased during 2 to 12 months following autologous MBT, remaining normal afterwards; in contrast, the levels of CD19+ lymphocytes and CD19+CD5+B-cells remained higher than normal ranges until 36 months in patients transplanted with allogeneic BM. The percentage of NK cells was significantly increased following both autologous and allogeneic BMT. The highest percentage of NK cells were detected about 2 and 6 months post-transplant in patients treated with autologous or allogeneic BM, respectively. CONCLUSIONS: Allogeneic BMT appears to induce a slight delay recovery of B and NK cells in comparison to autologous BMT. In contrast, T-cells recovery was similar for each type of transplant, although a higher percentage of CD3+CD5- T cells and a faster recovery of activated CD3+DR+ cells to normal levels were observed in patients transplanted with autologous BM.

Treatment of Ph1-positive chronic myelogenous leukemia in children: comparison between allogeneic bone marrow transplantation and conventional chemotherapy. Spanish Working Party for BMT in Children (GETMON).

BACKGROUND AND OBJECTIVE: To compare the estimated survival and disease-free survival between children with Ph1-positive chronic myeloid leukemia treated with allogeneic bone marrow transplantation or conventional chemotherapy. DESIGN AND METHODS: In this retrospective study we compared the results obtained in a group of 14 children who received allogeneic bone marrow transplantation (BMT) between 1983 and 1993, and another group of 27 children treated with busulfan, hydroxyurea or alpha-interferon during the same time period. Patients were transplanted at a median of 7 months from diagnosis and all except one were in their first chronic phase. Conditioning consisted in total body irradiation and cyclophosphamide in 12 cases, and busulfan was added in two. RESULTS: Of the 14 patients treated with BMT, two died of transplant-related complications and two relapsed 18 and 48 months after the BMT. Ten children remain alive and disease free at a median follow up of 60 months. The probability of DFS at 5 years is 70%. Of the 27 patients treated with chemotherapy, 22 have died at a median of 36 months from diagnosis. The probability of survival at 5 years is 5% versus 83% for the BMT group (p = 0.001). INTERPRETATION AND CONCLUSIONS: Allogeneic BMT is a safe and very effective treatment for Ph-positive CML in children. Patients who have an HLA-identical sibling donor must receive a transplant as soon as possible after being diagnosed.