Mismatched related donors of hematopoietic SCT (HSCT) for severe aplastic anemia (SAA) present challenges mainly associated with graft failure and GVHD. The greater the HLA disparity, the poorer the OS. About 19 consecutive SAA/very SAA (VSAA) patients who received HSCT from haploidentical family donors in our center are reported in this study, 18/19 pairs had 2-3 loci mismatched. All 19 cases failed to respond to previous therapy and were heavily transfused before transplantation. The conditioning regimen before HSCT included BU, CY and thymoglobulin. The recipients received CsA, mycophenolate mofetil (MMF) and short-term MTX for GVHD prophylaxis. The source of stem cell grafts was a combination of G-CSF-primed BM and G-CSF-mobilized peripheral blood stem cells. All patients achieved 100% donor myeloid engraftment; the median time for myeloid engraftment was 12 days (ranging from 10-29 days) and for platelets was 18 days (ranging from 8-180 days) with a cumulative platelet engraftment incidence of 84.21 ± 10.53%. The cumulative incidence was 42.1 ± 11.3% for grade II-IV acute GVHD and 56.2 ± 12.4% for chronic GVHD. The OS was 64.6 ± 12.4% with a median 746-day (90-1970) follow-up for surviving patients. These limited retrospective analysis data suggest that HLA-haploidentical HSCT for SAA patients without an HLA-identical sibling donor might be feasible. Further research to increase OS by decreasing GVHD while maintaining stable engraftment will be needed in the future.

and 5 The Jackson Laboratory, Bar Harbor, Maine, USA The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34 þ CD38À fraction. To understand the origin of malignant cells in primary human B-precursor acute lymphocytic leukemia (B-ALL), we established a novel in vivo xenotransplantation model. Purified CD34 þ CD38 þ CD19 þ , CD34 þ CD38ÀCD19 þ and CD34 þ CD38ÀCD19À bone marrow (BM) or peripheral blood (PB) cells from three pediatric B-ALL patients were intravenously injected into sublethally irradiated newborn NOD/ SCID/IL2rc null mice. We found that both CD34 þ CD38 þ CD19 þ and CD34 þ CD38ÀCD19 þ cells initiate B-ALL in primary recipients, whereas the recipients of CD34 þ CD38ÀCD10À CD19À cells showed normal human hematopoietic repopulation. The extent of leukemic infiltration into the spleen, liver and kidney was similar between the recipients transplanted with CD34 þ CD38 þ CD19 þ cells and those transplanted with CD34 þ CD38ÀCD19 þ cells. In each of the three cases studied, transplantation of CD34 þ CD38 þ CD19 þ cells resulted in the development of B-ALL in secondary recipients, demonstrating self-renewal capacity. The identification of CD34 þ CD38 þ CD19 þ self-renewing B-ALL cells proposes a hierarchy of leukemia-initiating cells (LICs) distinct from that of AML. Recapitulation of patient B-ALL in NOD/SCID/IL2rc null recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.

This study was performed to investigate incidence, causes and factors influencing mortality after haploidentical hematopoietic stem cell transplantation (HSCT) and to compare differences between haploidentical HSCT and HLA-identical sibling HSCT. From January 2000 to June 2011, 1411 patients with acute leukemia or myelodysplastic syndrome were included in this study. Of these patients, 571 received HLA-identical sibling HSCT and 840 received haploidentical HSCT. The cumulative incidence of overall mortality and transplant-related mortality (TRM) after haploidentical HSCT was higher than those after HLA-identical sibling HSCT (38.7% vs 33.3%, P = 0.012 and 27.5% vs 19.9%, P = 0.002), but the incidence of relapse-related mortality (RRM) did not differ between the two groups (15.6% vs 16.7%, P = 0.943). A multivariate analysis suggested that high-risk disease status and haploidentical HSCT correlated with a higher incidence of overall mortality (P o0.0001, hazard ratio = 1.911 and P = 0.019, hazard ratio = 1.249); in addition, in haploidentical HSCT, only high-risk disease status correlated with a higher incidence of overall mortality (P o0.0001, hazard ratio = 1.845). Our study suggested that haploidentical HSCT provided a higher incidence of overall mortality and TRM but the same incidence of RRM compared with HLA-identical sibling HSCT. Therefore, HLA-identical sibling HSCT remains the first choice, but haploidentical HSCT is available for patients without an HLA-identical sibling donor.

To study the efficacy and safety of a low dose of MTX combined with a low dose of methylprednisolone (MP) as a first-line therapy in the treatment of acute GVHD (aGVHD) after allogeneic hematopoietic SCT, 32 patients received i.v. MTX at a dose of 10 mg or oral MTX at a dose of 15 mg every 3-7 days (repeated at day 3 after the first dose and then at a weekly interval) combined with a low dose of MP (0.5 mg/kg/day) until a complete or partial response was achieved, or until treatment failure or intolerable side effects occurred. The overall treatment response rate was 81% (26/32 patients) and the response rate at day 28 was 75% (24/32 patients). The response rate for GVHD involving various organs was 88% (23/26) in the skin, 75% (3/4) in the liver and 81% (9/11) in the gut. Grade 3 toxicities occurred in only three patients presenting cytopenias. The estimated survival at 2 years was 77%. From this analysis, MTX in combination with a low dose of MP appears to be a well-tolerated, effective and inexpensive regime when used as a first-line treatment for aGVHD.