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Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft. Haploidentical transplant modalities are based mainly on high-intensity conditioning regimen, but reduced intensity regimens have recently been introduced. The graft may be a megadose of extensively T cell-depleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of GVHD- and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling. Improvements will come with successful implementation of strategies to accelerate and strengthen post transplant immune reconstitution as well as transplantation of patients in early stage disease.Bone Marrow Transplantation (2008) 41, 473–481; doi:10.1038/sj.bmt.1705966; published online 7 January 2008 [ABSTRACT FROM AUTHOR]

T cell-depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia-free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor analysis was performed for patients who underwent transplantation in remission (n = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased RI was observed for children given a graft with higher number of CD34(+) cells (adjusted P = .09 and P = .07, respectively). In a multivariate analysis, haploHSCT performed in larger centers (performing > or = 231 allotransplantations in the studied period) was associated with improved LFS rate and decreased RI (adjusted P = .01 and P = .04, respectively), adjusting for different patient-, disease-, and transplant-related factors such as number of previous autotransplantations, cytomegalovirus serology status, type of T-cell depletion, and use of total body irradiation and antithymocyte globulin. In conclusion, higher CD34(+) cell dose and better patient selection may improve outcomes of children with ALL who undergo a haploHSCT. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers.

In autologous and allogeneic hematopoietic SCT (HSCT) neutropenia may be associated with severe infection. Immunodeficiency associated with GVHD and its treatment in allogeneic HSCT is also a risk for severe infection. In both periods, patients may develop severe sepsis with organ failure. To gain insights into treatment possibilities, HISTORY, a multicenter retrospective study reviewed HSCT patient records on mortality, organ dysfunction, platelet count and bleeding events. All transplantation records from 16 European centers were reviewed for 1.5 years. Of 2092 patients screened, 160 were documented for HSCT with respiratory and/or cardiovascular organ dysfunction because of sepsis and/or GVHD. Mortality was 53.1% at 28 days and 65.6% at 100 days. HSCT patients with sepsis and organ dysfunction are at highest risk of death (49.5%). Death from refractory septic shock was 15.2%, and it was 20% from respiratory failure and 64.7% from sepsis. Fewer than 3% of HSCT patients died from bleeding complications; however, individuals at increased risk of bleeding were excluded. Despite low platelet counts, an increased risk of bleeding could be established only if thrombocytopenia dropped below 13 x 10(9)/l. Thus, there might be a therapeutic window for treatment strategies for severe sepsis in HSCT, such as drotrecogin alpha (activated).

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative treatment to patients with high-risk acute leukemia lacking a human leukocyte antigen-matched donor. We analyzed 173 adults with acute myeloid leukemia (AML) and 93 with acute lymphoblastic leukemia (ALL) who received a haplo-HSCT in Europe. All grafts were T cell-depleted peripheral blood progenitor cells from a direct family or other related donor. At transplantation, there were 25 patients with AML in CR1 (complete remission 1), 61 in more than or equal to CR2, and 87 in nonremission, and 24 with ALL in CR1, 37 in more than or equal to CR2, and 32 in nonremission. Median follow-up was 47 months in AML and 29 months in the ALL groups. Engraftment was observed in 91% of the patients. Leukemia-free survival at 2 years was 48% plus or minus 10%, 21% plus or minus 5%, and 1% for patients with AML undergoing transplantation in CR1, more than or equal to CR2, and nonremission, and 13% plus or minus 7%, 30% plus or minus 8%, and 7% plus or minus 5% in ALL patients, respectively. In conclusion, haplo-HSCT can be an alternative option for the treatment of high-risk acute leukemia patients in remission, lacking a human leukocyte antigen-matched donor.