Partially mismatched related-donor bone marrow transplantation for pediatric patients with acute leukemia: younger donors and absence of peripheral blasts improve outcome.

PURPOSE: To extend access to bone marrow transplantation (BMT), we used partially mismatched related donors (PMRD) for pediatric patients with acute leukemia. In this report we sought to determine pretransplantation factors that might predict outcome. PATIENTS AND METHODS: Of 67 such patients, 43 had acute lymphocytic leukemia and 24 had acute myelogenous leukemia. At the time of transplantation, 41 patients were in relapse. Donors included 40 parents, 24 siblings, and three cousins. HLA disparity of two to three major antigens was detected in two thirds of the donor-recipient pairs. Conditioning therapy, including total-body irradiation and chemotherapy followed by graft-versus-host disease (GvHD) prophylaxis with partial T-cell depletion of the graft using T10B9 or OKT3, was combined with posttransplantation immunosuppression. RESULTS: Estimated probability (EP) of engraftment was 0.96 and was not affected by donor-antigen mismatch (AgMM; P =.732). EP of grades 2 to 4 acute GvHD was 0.24 and was not affected by recipient AgMM (P =.796). EP of disease-free survival was 0.26 at 3 years but improved to 0.45 when donors were younger than 30 years (P<.001). EP of relapse at 3 years was 0.41 and reduced with younger donors' age. For patients who were in relapse at the time of transplantation, absence of blasts was associated with a lower relapse rate (0.46 v. 0.84; P =. 083), similar to that of patients in remission. CONCLUSION: PMRD-BMT in pediatric leukemia resulted in high engraftment and low GvHD rates. To improve outcomes, younger donors should be sought, and clinicians should attempt to reduce peripheral blasts in patients who are in relapse.

Use of partially mismatched related donors extends access to allogeneic marrow transplant.

Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has been made available for approximately 50% of Caucasians and less than 10% of ethnic and racial minorities in need. However, almost all patients have a readily available partially mismatched related donor (PMRD). We summarize our experience with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who were recipients of a PMRD allo-BMT from haploidentical family members following conditioning therapy using total body irradiation (TBI) and multiagent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patients. There was a statistically significant difference in 2-year survival probability between low-risk and high-risk patients (0.55 v 0.27, P = .048). Prognostic factors that affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P = .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a high-risk disease category increased treatment failure from relapse or death (P = .037). A PMRD transplant can be performed with acceptable rates of graft failure and GVHD. Using sequential immunomodulation, the disease status at the time of transplant is the only prognostic factor significantly associated with long-term successful outcome after PMRD allo-BMT. When allogeneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclusion of all ethnic or racial groups.