No abstract

Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.

Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non-Tcell-depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLAidentical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P ‫؍‬ .0006).

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation. In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) were enrolled between August 1999 and June 2004. All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.

Summary:A prospective longitudinal study of cognitive and psychosocial functioning in pediatric hematopoietic stem cell transplant (HSCT) patients was conducted on three occasions: pre-HSCT, 1 year post-HSCT, and 2 years post-HSCT. In contrast to the previous hypothesis that cognitive declines would occur as a result of HSCT treatment, it was hypothesized that (1) global cognitive functioning (IQ scores), as well as specific areas would remain stable over time; (2) pre-transplant functioning would be predictive of later functioning; and (3) age would be negatively related to cognitive functioning. Based on previous research it was further hypothesized: that (4) while declines in psychosocial functioning might be seen at 1 year, functioning would improve by 2 years. 153 children and adolescents were evaluated pre-HSCT and at 1 year, with 2 year data available for 74 children. Advances in pediatric hematopoietic stem cell transplantation (HSCT) have resulted in increased survival and greater attention to long-term effects of treatment. Mortality remains relatively high in this population, however, and accumulation of data from a sufficient number of patients who survive this treatment involves many years. As a result, our understanding of the cognitive and behavioral Correspondence: MJ Kupst,

Alternative donor bone marrow transplantation (BMT) to treat severe aplastic anaemia (SAA) in children and young adults has been complicated by high rates of graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that increased immunosuppression combined with T-cell depletion of the marrow graft would enable successful use of unrelated donor BMT in this disease. Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9. GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January 1996, 15/28 (54%) patients are alive, transfusion independent and well with a range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities include all three patients with nonengraftment and all three patients with grade III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity. The incidence >or= grade II acute GVHD was 28%. These data show that in children with SAA who have failed immunosuppression, unrelated donor BMT offers a reasonable hope of long-term survival.

The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigenmismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P ‫؍‬ .01) and mismatched unrelated patients (26%, P ‫؍‬ .014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P ‫؍‬ .01) and haploidentical grafts (42%, P ‫؍‬ .001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%, P ‫؍‬ .01) or haploidentical (21%, P ‫؍‬ .002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor. (Blood. 2002;99:806-814)

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.