Early hematopoietic stem cell transplant is associated with favorable outcomes in children with MDS.

BACKGROUND: Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for childhood myelodysplastic syndrome (MDS), there is no consensus regarding patient or disease characteristics that predict outcomes. PROCEDURE: We reviewed 37 consecutive pediatric MDS patients who received myeloablative HSCT between 1990 and 2010 at a single center. RESULTS: Twenty had primary MDS and 17 had secondary MDS. Diagnostic cytogenetics included monosomy 7 (n = 21), trisomy 8 (n = 7) or normal/other (n = 8). According to the modified WHO MDS classification, thirty had refractory cytopenia and seven had refractory anemia with excess blasts. IPSS scores were: low risk (n = 1), intermediate-1 (n = 15), and intermediate-2 (n = 21). OS and DFS at 10 years in the entire cohort was 53% and 45%. Relapse at 10 years was 26% and 1 year TRM was 25%. In multivariate analysis, factors associated with improved 3 years DFS were not receiving pre-HSCT chemotherapy (RR = 0.30, 95% CI 0.10-0.88; P = 0.03) and a shorter interval (<140 days) from time of diagnosis to transplant (RR = 0.27, 95% CI 0.09-0.80; P = 0.02). Three years DFS in patients who did not receive pre-HSCT chemotherapy and those who had a shorter interval to transplant (n = 16) was 80%. CONCLUSION: These results suggest that children with MDS should be referred for allogeneic HSCT soon after diagnosis and that pre-HSCT chemotherapy does not appear to improve outcomes.

Use of infliximab-daclizumab combination for the treatment of acute and chronic graft-versus-host disease of the liver and gut.

Infliximab-daclizumab was used to treat acute and chronic liver and gut graft-versus-host disease (GVHD) in two children after standard immunosuppressive therapy failed. Infliximab (10 mg/kg weekly, 4 doses) and daclizumab (1 mg/kg, days 1, 4, 8, 15, and 22) were given over 1 month. In case 1, grade 2 chronic GVHD of the liver developed 1 year after transplantation and failed to improve with tacrolimus, mycophenolate mofetil, and prednisone. In case 2, corticosteroid-unresponsive grade 3 acute liver and gut GVHD developed on day +37. In both patients, GVHD responded to the infliximab-daclizumab regimen without toxicity and immunosuppressive therapy was discontinued.

Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia.

In four patients, aged 15 - 20 years, with high-risk acute myeloid leukemia (AML), high-dose samarium 153-labelled ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) was used for targeted marrow irradiation before preparative chemotherapy conditioning regimens and allogeneic (three patients) or autologous (one patient) hematopoietic stem cell transplantation. The dose of 153Sm-EDTMP was 703 MBq/kg (n = 1) or 1110 MBq/kg (n = 3). No side-effects occurred during the 30-min infusion of 153Sm-EDTMP. Samarium - melphalan regimens were given to three patients; one had 153Sm-EDTMP - busulfan + cyclophosphamide. Total body radioactivity was below the 133 MBq safe limit before infusion of stem cells (day 14 after 153Sm-EDTMP). No hemorrhagic cystitis, nephrotoxicity or serious infections occurred. Leukocyte engraftment (white blood cell count >0.5 x 10(9)/l) occurred between 12 and 23 days after stem cell infusion (mean of 17 days). Complete cytogenetic and morphologic remission of AML was evident on follow-up marrow aspirate and biopsy specimens from all patients. In two of the four study patients, the disease remains in complete remission and the patients have an excellent quality of life (Eastern Cooperative Oncology Group performance status 0; no medications) and no organ toxicity more than 2 years and more than 4 years, respectively, after their blood and bone marrow transplantations. Thus, in adolescents and adults, 153Sm-EDTMP may provide a relatively simple and effective means for using irradiation to eliminate AML within the marrow.