Allogeneic hematopoietic cell transplantation from alternative donors in children with myelodysplastic syndrome: is that an alternative?

Allogeneic hematopoietic cell transplantation (HCT) in children with myelodysplastic syndrome (MDS) remains a challenge due to the toxic conditioning regimens administered to minimize the risk of relapse in the HLA-matched or of graft rejection in the HLA-mismatched settings. In the absence of matched sibling donors, alternative donors such as unrelated and/or partially matched family sources remain risky, yet the only available, options. Herein we report the results of HCT from alternative donors in 14 children with different subtypes of MDS (juvenile myelomonocytic leukemia [JMML] n = 9; myelodysplastic syndrome [MDS] refractory anemia n = 3; MDS refractory anemia with excess of blasts in transformation n = 2) transplanted at our institution. The median time from diagnosis to HCT was 9 months (range 4 to 90 months). The variety of HCT types included: unrelated peripheral blood progenitor cell transplantation (PBPCT) (n = 2), partially matched family donor T-cell-repleted BMT/PBPCT (n = 6), and haploidentical T-cell-depleted PBPCT (n = 6). Five of 14 patients remain alive at 7 to 37 months posttransplant (including two patients after partially matched family donor BMT, two patients after haploidentical T-cell-depleted-PBPCT, and one after unrelated-PBPCT, respectively). The major complications were: primary graft failure in the haploidentical T-cell-depleted-setting or graft-versus-host disease (GvHD) in T-cell-repleted partially matched family or unrelated settings, respectively. Despite the high transplant-related mortality rate in this series, allogeneic HCT from alternative donors remains an interesting solution for children with MDS who lack matched sibling donors. Due to improved immune reconstitution, despite an increased risk of GvHD, T-cell-repleted transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors. Splenectomy prior to HCT may positively affect the posttransplant course in patients with overt splenomegaly for example those afflicted with JMML.

Prognostic significance of DNA di-tetraploidy in neuroblastoma.

BACKGROUND: Identification of biological factors may provide tools to discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer risk adapted treatment intensity. PROCEDURES: Tumour cell DNA content, MYCN amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well as three serological markers were assessed in 179 children with neuroblastoma. RESULTS: Localised regional disease (stage 1 to 3) was diagnosed in 98 patients, and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s). Median age at diagnosis was 12 months and the median observation time 4 years. Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a significantly worse prognosis of 44% overall survival at 4 years in comparison with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed a significant correlation with additional adverse biological factors (NMA, del 1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on the overall (OS) and event free survival (EFS) estimations revealed that near di-tetraploidy was the most powerful biological factor, with a P-value of <0.001 for EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS. CONCLUSIONS: This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.

High-dose chemotherapy with autologous hematopoietic progenitor cell transplantation in children with high-risk NHL and ALL-preliminary results.

Since May 95 to December 97 twenty children with NHL (n=14, NHL B = 11, NHL NB = 3) or ALL (n=6, high risk n=2, standard risk n=4) underwent high-dose chemotherapy with subsequent autologous hematopoietic progenitor cells transplantation. In 19 children progenitor cells were harvested with the use of Fenwal CS3000 Plus cell separator from the peripheral blood after cytotoxic mobilization with G-CSF (Neupogen 5 microg/kg). One patient received PBPC and autologous bone marrow. One patient received positively selected CD34+ cells (CeprateSC, CellPro). One patient received autologous marrow purged with mafosfamide. All patients with NHL received conditioning according to BEAM protocol. Patients with ALL were conditioned with BU,CY,VP, BU,CY or BU. The median number of transplanted CD34+ cells was 3.84x10(6) (0.51x10(6)-74.7x10(6)). Children transplanted with unmanipulated hematopoietic progenitor cells recovered in granulocytes >500/microl at a median time of 12 days (range from 9 to 28 days). Platelet recovery >50000/microl was observed at a median time of 26 days (range from 13 to 347days). Sixteen children (80 %) are alive and well in continuous complete remission from 4 to 36 months after transplantation (median +20). Three children (15%) relapsed and died because of the disease. One patient died in complete remission on day +41 because of aspergillosis. Transplant related mortality was 5,0%. Overall survival was 79%. Event free survival was 86% in NHL and 67% in ALL.