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Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts.

Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts. [ABSTRACT FROM AUTHOR]

Acute Graft-versus-Host-Disease (aGvHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (HSCT). Although rather helpful, the use of conventional immunosuppressive drugs leads to general immunosuppression and is toxic. The effects of CD4+ T-cells, in respect to the development of aGvHD, can be altered by administration of antihuman CD4 monoclonal antibodies, here MAX.16H5 IgG1. This approach must be tested for possible interference with the Graft-versus-Leukemia-Effect (GvL). Thus, in vitro experiments were conducted, exposing P815 leukemic cells to bone marrow and splenocytes from cd4−/−-C57Bl/6 mice transgenic for human CD4 and HLA-DR3 (triple transgenic mice, [TTG]) as well as previously irradiated splenocytes from Balb/cwt mice. Using flow cytometry, the vitality of the various malignant and graft cells was analyzed over the course of 4 days. The survival rate of P815 cells did not change significantly when exposed to MAX.16H5 IgG1, neither did the viability of the graft cells. This provides evidence that MAX.16H5 IgG1 does not impair the GvL effect in vitro. Additionally, P815-Balb/cwt leukemic mice were transplanted with P815GFP cells, bone marrow, and splenocytes from TTG mice with and without MAX.16H5 IgG1. Without transplantation, P815GFP leukemic cells could be detected by flow cytometry in the liver, the bone marrow, and the spleen of recipients. The antibodies prevented aGvHD while leaving the GvL effect intact. These findings indicate no negative effect of MAX.16H5 IgG1 on the GvL effect in vitro and in vivo after HSCT in a murine model. © 2015 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic stem cell transplantation is a curative treatment option for many hematological diseases, and the numbers of transplantations are steadily increasing worldwide. Major progress has been made in lowering treatment-related mortality by reducing intensity of the conditioning regimen and by improving supportive care (eg, for infectious complications). Accordingly, relapse after allogeneic stem cell transplantation has become the major cause for treatment failure. Major efforts to prevent or treat relapse are focused on cellular- (T cell, natural killer cell), cytokine-, or antibody-based strategies to enhance the graft-versus-tumor effect or circumvent immunoescape. In the more recent years, new classes of agents have shown activity in several hematological malignancies, and besides their immediate antitumor activity, most of them also possess immune-modulatory qualities that may be useful alone or in combination with adoptive immunotherapy after allogeneic stem cell transplantation to enhance graft-versus-tumor effects. Here, we summarize the current knowledge and potential use of 2 of these compounds in preventing or treating relapse after allogeneic stem cell transplantation, namely immune-modulating drugs and hypomethylating agents. [Copyright &y& Elsevier]

We describe the first reported Klinefelter's syndrome (KS) in which allogeneic bone marrow transplantation from an unrelated donor (UR-BMT) was performed for treatment of chronic myelogenous leukemia in blast crisis (CML-BC). A 31-year-old male patient was diagnosed as having CML-BC with KS in April 2001. The result of a bone marrow chromosomal examination were 47, XXY, t(9;22)(q34;q11). After he had been treated with chemotherapy and imatinib mesylate, he underwent UR-BMT in February 2002. After the UR-BMT, his bone marrow chromosome changed from 47, XXY, t(9;22)(q34;q11) to 46,XY and 100% donor-type chimerism was obtained. However, he relapsed on day 83 after UR-BMT. After treatment with imatinib mesylate and tapering of immunosuppressive agents, skin and liver GVHD developed and then donor-type chimerism was increased with decreased blast cells. However, the patient died due to progression of disease in October 2002. [ABSTRACT FROM AUTHOR]