Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

[Severe acquired aplastic anemia: historical outcome of patients treated by allogeneic bone marrow transplantation from matched sibling donors. A study by the Spanish Group for Bone Marrow Transplantation in Children (GETMON)]. / Aplasia medular grave adquirida: evolución histórica de los resultados obtenidos con trasplante de progenitores hematopoyéticos de donante familiar. Estudio del Grupo Español para el Trasplante de Médula Osea en Niños (GETMON).

INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation is the treatment of choice for acquired aplastic anaemia in children. Experience with this approach from Spanish Working Party for Bone Marrow Transplantation in Children in two sequential time periods (1982-1990 and 1991-2004) is reported. PATIENTS AND METHODS: Sixty two consecutive patients with a median age of 10 years were transplanted; 18 in the 1982-1990 period and 44 in the 1991-2004 period. Conditioning regimen consisted mainly of irradiation and cyclophosphamide in the first period (72 % of patients) and cyclophosphamide +/- anti-thymocyte globulin (62 %) in the second. Graft versus host disease prophylaxis consisted of cyclosporine in most patients (57/62). RESULTS: Fifty one patients are alive and disease-free at a median follow-up of 127 months. Five years probability of event-free survival is 82 %. The survival increased from 61 % to 91 % during the two time periods. Eleven patients died from graft failure or rejection (3), acute or chronic graft versus host disease and infection (4) or multi-organ failure (4). Univariate analysis identified two significant prognostic factors: interval diagnostic/transplant and time period of transplant (for both p = 0.03). CONCLUSIONS: This experience corroborates that allogeneic haematopoietic stem-cell transplantation is the best treatment for severe acquired aplastic anaemia, with a current disease-free survival of 90 % of patients.

[Long and medium-term neuropsychological sequelae of bone marrow transplantation in pediatric patients with hematological disease]. / Secuelas neuropsicológicas a medio y largo plazo del trasplante de medula ósea en pacientes con enfermedades hematológicas.

BACKGROUND: Few studies exist on the neuropsychological sequelae of bone marrow transplantation (BMT) in pediatric patients. Published results show considerable discrepancies although studies of children with acute lymphoblastic leukemia undergoing high doses of cranial radiotherapy report short- and long-term loss of cognitive ability. OBJECTIVES: To determine the effects of BMT and the effect of anxiety on the pre-BMT assessment in a group of children with severe hematological disease treated in our center. METHODS: We performed a descriptive, prospective, longitudinal study of 54 children, aged 4-15 years, who were treated between 1987 and 1995. Twenty-two children were evaluated before and after BMT by means of the Weschler Intelligence Scale. To control for the effect of anxiety on the pre-BMT scores, the patients were divided into two groups according to the scores obtained in this test (group 1: IQ score 100; group 1: IQ100). RESULTS: Comparison of pre- and post-BMT scores for both groups revealed no significant differences. However, comparison of the results between groups revealed that group I scored lower in the post-BMT test than in the pre-BMT test while group I scored higher in the post-BMT test than in the pre-BMT test. CONCLUSIONS: Although comparison between the pre- and post-BMT results obtained from the whole sample showed no differences that indicated post-treatment sequelae, treatment-induced anxiety may have influenced the pre-BMT score.

[Transplantation of umbilical cord blood hematopoietic progenitor cells in children]. / Trasplante de progenitores hematopoyéticos de sangre de cordón umbilical en niños.

AIM: Retrospective study of the outcome of cord blood transplantation (CBT) in children in Spain. METHODS: Twenty-eight patients (mean age 6.5 years; mean weight 25 kg) received a CBT between July 1994 and May 1998 in several centres of the Spanish Pediatric Bone Marrow Transplant Group. In 2 patients the donor was an identical human leukocyte antigen (HLA)-sibling and in two the donor was a mismatched family donor. In 24 patients the donor was unrelated, and 21 of these received an HLA-mismatched CBT. Twenty-one patients (75 %) received a CBT for leukemia mainly in advanced phase. Seven patients were transplanted for genetic disease. Of these, five had congenital immunodeficiency. The conditioning treatment included total body irradiation in ten patients and combined chemotherapy in the remaining patients. In all patients graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine, and corticosteroids or methotrexate were added in patients with HLA-mismatched donors. The mean number of nucleated cells infused was 53.4 x 106/kg. RESULTS: Graft failure was observed in nine patients. Eighteen patients (64.3%) developed grade IIIV acute GVHD. Eight patients (28.6%) developed severe GVHD. Actuarial event free survival (EFS) of all the patients was 34.4 +/- 9% at 3 years, with a mean followup of 16.6 months. EFS was more favorable in patients with genetic disease (71>=6 17%) and in those with an HLA (A, B and DR) identical donor (6/6) (66>=6 19%). CONCLUSIONS: The most favorable results were obtained in patients with genetic diseases. We observed an inverse correlation between EFS and patients with HLA identical donors. The high incidence of severe acute GVHD could have been related to a lack of accuracy in the HLA typography of some patients.

Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group.

We have analyzed factors influencing the outcome of 102 children with acute leukemia given a cord blood transplantation (CBT) and reported to the Eurocord Registry. Seventy patients with acute lymphoblastic and 32 with acute myeloid leukemia were given either a related (n = 42) or an unrelated (n = 60) CBT. Children given CBT during first or second complete remission were considered as belonging to the good-risk group (n = 66), whereas those who received a transplant in a more advanced stage of disease were assigned to the poor-risk group (n = 36). In the related group (RCBT), 12 of 42 patients received transplantation from an HLA-disparate donor, whereas in the unrelated group (UCBT) 54 of 60 received an HLA mismatched CBT. Kaplan-Meier estimates for neutrophil recovery at day 60 were 84% +/- 7% in RCBT and 79 +/- 6% in UCBT (P =.16). In multivariate analysis, the most important factor influencing neutrophil engraftment in UCBT was a nucleated cell dose infused greater than 3.7 x 10(7)/kg (P =.05, relative risk [RR] of 1.85, 95% confidence interval [CI]: 0.98-3.4). The incidence of grade II through IV acute graft-versus-host disease was 41% +/- 8% in the RCBT group and 37% +/- 6% in the UCBT group (P =.59). Kaplan-Meier estimates of 2-year event-free survival (EFS) after RCBT or UCBT were 39% +/- 8% and 30% +/- 7%, respectively (P =.19). In multivariate analysis, the most important factor influencing EFS was disease status at time of transplantation: good-risk patients had a 2-year EFS of 49% +/- 7% as compared to 8% +/- 5% in patients with more advanced disease (P =.0003, RR: 0.40, 95% CI: 0.24 to 0. 65). This was a consequence of both an increased 1-year transplant related mortality and a higher 2-year relapse rate in the poor-risk group (65% +/- 9% and 77% +/- 14%, respectively), as compared with good risk patients (34% +/- 6% and 31% +/- 9%, respectively). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.

[Allogeneic bone marrow transplantation in children with severe acquired aplastic anemia. The long-term results. The Spanish Group for Bone Marrow Transplantation in Children (GETMON)]. / Transplante alogénico de médula ósea en niños con aplasia medular grave adquirida. Resultados a largo plazo. Grupo Español para el Trasplante de Médula Osea en Niños (GETMON).

OBJECTIVE: The objective of this study was to evaluate retrospectively the efficacy of allogeneic BMT in the treatment of childhood severe acquired aplastic anemia (SAAA). PATIENTS AND METHODS: Twenty-seven children aged 2 to 16 years (median 11 years) received a BMT from an HLA identical sibling. Conditioning consisted in irradiation (total, nodal or thoraco-abdominal) plus cyclophosphamide (120-200 mg/kg) in 15 patients and cyclophosphamide alone (200 mg/kg) in the rest. Prophylaxis for graft-versus-host disease (GVHD) was cyclosporine and methotrexate in most patients. RESULTS: Twenty-four children achieved the bone marrow graft at a median of 18 days (neutrophils) and 21 days (platelets). Two patients failed engraftment and 1 had a late graft rejection. Three patients developed acute GVHD grades 3-4 and six chronic GVHD, which was extensive in 4 of them. Twenty patients/71%) are alive and disease-free at a median follow-up of 110 months and the estimated disease free survival at 6 years is 67%. CONCLUSIONS: Our results confirm that allogeneic bone marrow transplantation from an HLA identical sibling is the best treatment modality for children with SAAA. Acute GVHD associated with infections and graft rejection were responsible for treatment failures.