Work

Promising outcomes of allogeneic cord blood transplant (CBT) for high risk acute lymphoblastic leukemia (ALL) in children

Year: 2005

Type: article

Abstract: Background: Optimal therapy for high risk and relapsed acute lymphoblastic leukemia (ALL) remains uncertain. Wider availability of cord blood from related and unrelated donors has prompted studies of its use for hematopoietic stem cell transplant (HSCT). Graft rejection and lack of graft versus leukemia (GVL) effect could be drawbacks to CBT. In contrast, possible reduction in morbidity and mortality from graft versus host disease (GVH) argue for CBT. Procedure: We evaluated 26 consecutive cord blood transplants (CBT) for ALL performed at our center from 1996–2002 on studies using consistent conditioning therapy and graft-versus-host disease (GVHD) prophylaxis. Indications for CBT were CR1 with high risk cytogenetics (Ph+, MLL rearrangement; N=9), CR2 following marrow relapse on therapy or <1 year off (N=10), CR3 or relapse with limited marrow disease (N=5). Median patient age was 8.5 years (Range, 0.5–24 y). CB was from unrelated donors (N=25) and a matched sibling donor (N=1). Among the unrelated donors, HLA matching was 6/6 (N=6), 5/6 (N=11), and 4/6 (N=8). Median infused total nucleated cell dose per kilogram (TNC/kg) was 3.26e7 (Range, 0.8–12.9e7). GVH prophylaxis consisted of cyclosporine and methylprednisolone (N=25) and cyclosporine alone (N=1; matched sib CBT). Results: With median follow-up of 548 days, 16/26 patients (62%) are event-free survivors (EFS). Six events were due to toxicity and/or infectious complications. Four events were due to relapse. Median time to event was 115 days (Range, 14–728 d.). ANC >500/mm3 occurred at a median of 23.5 days post-CBT (Range, 14–61 d.). Platelet count >20,000/mm3 without transfusion occurred at 65 days (Range, 25–222 d.). Acute GVHD developed in 14/24 evaluable patients, reaching grade III-IV in 7 patients. Chronic GVHD occurred in 10/22 evaluable patients. Multivariate analysis showed higher infused TNC/kg to be the strongest predictor of EFS. CR number at HSCT, degree of HLA match, time to neutrophil engraftment, time to platelet engraftment, and acute or chronic GVHD were not significant predictors of EFS in univariate analysis. Age was a significant EFS predictor in univariate analysis, however lost its significance in multivariate analysis when TNC/kg was included. Conclusions: We conclude that CBT can effectively treat ALL in children with high risk features and following relapse. Survival benefits may derive from more manageable GVHD with retention of adequate graft-versus-leukemia effect.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2004.12.179