Intravenous ribavirin for respiratory syncytial viral infections in pediatric hematopoietic SCT recipients.

Respiratory syncytial virus (RSV) is a potential cause of serious morbidity and even mortality among children undergoing hematopoietic SCT (HSCT). Contrary to the available information regarding the aerosolized formulation of ribavirin, there is a paucity of published studies using i.v. ribavirin in adults, and very few single reports on pediatric patients. Aerosolized drug administration has been limited by potential toxicity and special air-flow requirements. In this regard, i.v. ribavirin could prevent these disadvantages, but its efficacy and safety remain controversial in the pediatric HSCT setting. The present study describes the outcome of six pediatric patients undergoing HSCT with nine episodes of proven RSV. Four episodes corresponded to lower respiratory tract infection (LRTI) and five presented with upper respiratory tract infection (URTI). All LRTI patients showed favorable clinical responses, with 100% survival and no progression to LRTI in the remaining five URTI. No side effects were documented during ribavirin administration. We conclude that ribavirin was well tolerated intravenously, without associated side effects, and was effective in the treatment of RSV in this limited number of pediatric HSCT patients. The role and efficacy of i.v. ribavirin needs to be further clarified by prospective controlled trials in pediatric populations.

Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience.

We studied surveillance, incidence and outcome of viral infections in children undergoing allogeneic hematopoietic cell transplantation (HCT) in the main pediatric transplant units in Spain. We prospectively collected data from first year post-HCT in every consecutive allogeneic HCT performed during 3 years (N = 215): first HCT = 188 and second HCT = 27; median age = 6.6 years (0.1-20.7). Most patients had acute leukemia (N = 137) and 135 recipients (63%) were CMV seropositive. A total of 46 patients underwent cord blood transplant, 133 patients underwent HCT from alternative donors (62%) and 101 patients received anti-thymocyte globulin. Observational time was completed in 137 patients, whereas the remaining 78 died after a median survival time of 99 days (3-352). CMV was monitored in all patients; adenovirus (ADV) and human herpesvirus 6 (HHV-6) were monitored in 101 and 33 patients, respectively. We found 145 viral infections in 103 patients: CMV (n = 42), ADV (n = 32), HHV-6 (n = 7), polyomavirus (n = 20), EBV (n = 6), VZV (n=17) and others (n = 8). CMV infection was significantly higher in seropositive patients (25 vs 7%) (P = 0.02). Extensive chronic GVHD (cGVHD) was significantly associated with an increased rate of viral infections (12 of 16 patients with cGVHD had infections vs 91 of 199 without GVHD) (P = 0.035). In total, 10 patients (4.6%) died of viral infections (CMV = 5, ADV = 3, respiratory = 2). We found a high incidence of viral infection, but mortality was low.

High rate of long-term survival for high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

Patients with high-relapse-risk lymphomas or those relapsing after initial therapy have a limited probability of cure with conventional treatment. There is recent inconclusive evidence that, in such cases, intensification or salvage treatment with high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) increases the response rate and may improve survival. Nevertheless, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 101 consecutive patients receiving high-dose chemotherapy followed by HSCT after induction with standard chemotherapy. The median age was 38 years (range, 12-63 years). The diagnoses were Hodgkin's disease (n = 32), follicular lymphoma (n = 33), diffuse large B-cell lymphoma (n = 12), mantle cell lymphoma (n = 7), T-cell lymphoma (n = 14), and others (n = 3). Patients received either an autologous graft (n = 72) in first complete remission (1CR; n = 23) or in advanced stages (AS; n = 49), or an allogeneic graft (n = 29) in 1CR (n = 7) or in AS (n = 22). We concluded that transplant-related mortality was 2.7% for patients receiving an autologous HSCT and 27% for patients receiving an allogeneic HSCT. The main etiologies were graft-versus-host disease and infection in the allogeneic setting, and infection in the autologous setting. The probability of long-term (12-year) overall survival was 71%, higher than that described for high-relapse-risk lymphoma patients treated without HSCT and significantly better (P < .05) for patients who received the transplant in 1CR (89%) than in AS (65%). Finally, the probability of long-term survival was significantly better for patients treated with HSCT during the period from 2000-2007 (85%) compared with the period from 1989-1999 (72%).

[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.

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).

Hemopoietic stem cell transplantation in childhood: reduction in mortality and improvement of survival over the years.

Stem cell transplantation (SCT) is an effective treatment for life-threatening hematologic and nonhematologic pediatric diseases. Reducing transplant-related mortality (TRM), a major complication of SCT, to improve long-term survival, therefore, is one of the main objectives of transplantation teams. We analyzed TRM and overall survival (OS) over the years in children undergoing SCT in our center. From June 1998 to October 2002, 156 consecutive children, 105 boys and 51 girls, median age 10 years (range, 2-18), with different diagnoses underwent SCT (100 autologous and 56 allogeneic). OS and TRM were analyzed in 2 different periods (June 1989-December 1998 and January 1999-October 2002) and grouped according to the different SCT modalities. The median follow-up was 18 months (range, 1-160). Autologous TRM showed a statistically significant improvement within 1999-2002 (0%) compared with 1989-1998 (12.2%) (P < .05). There were no statistical differences for allogeneic SCT. OS was 34% in the first period and 80.4% in the second period (P < .01), the improvement being for both autologous and allogeneic SCT. In our study, TRM decreased significantly for those children receiving autologous SCT in recent years. OS was significantly better in the latter period (1999-2002), both globally and for each SCT modality.

A fully automated method for mononuclear bone marrow cell concentration.

We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS-3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases. Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU-GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31-98.6% vs. 80.34-98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1,000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS-3000 processor is an efficient method for fully automated large-scale processing of human bone marrow cells.