Post Transplant High-Dose Cy as GvHD Prophylaxis in 1 HLA Mismatched Unrelated HSCT for Myeloid Malignancies
Condition: Myeloid Malignancies
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The experimental treatment consists in the application of a therapeutic strategy with post
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation
      for Myeloid Malignancies.
    

Detailed description: 
      The experimental treatment consists in the application of a therapeutic strategy with post
      Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving
      1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation
      for Myeloid Malignancies Allogeneic hematopoietic stem cell transplantation is a potentially
      curative therapy for a variety of hematologic malignancies due to two separate components:
      chemo/radiotherapy administered before the transplant (conditioning regimen) and the presence
      of immunocompetent cells in the graft, capable of inducing a "graft-versus-malignancy effect"
      also known as "GvL" effect. However, this immune-reaction usually carries the risk of
      detrimental effects seen as a multi-organ syndrome known as graft-versus-host disease (GvHD),
      which remains the most feared complication of Allogeneic hematopoietic stem cell
      transplantation. GvHD may be given to disparities between donor and recipient in presence of
      gene mismatches in the Major Histocompatibility Complex, also known as Human Leucocyte
      Antigen (HLA) system, or in any minor histocompatibility antigen. Thus, GvHD is obviously
      more common (and possibly more severe) in patients transplanted from HLA-mismatched donors as
      compared with those receiving grafts from HLA-matched donors.

      A major limitation of allo-HSCT is the availability of a donor given that only a small
      percentage of patients has a HLA identical family donor. For the majority of patients
      (approximately 70%) who lack a HLA-identical sibling, alternative donors include HLA-matched
      unrelated donors and cord blood units. The chance of identifying a suitable marrow unrelated
      donor (MUD) in the international voluntary donor registries is limited by the frequency of a
      certain HLA genotype in the general population.

      One of the alternative options in such cases is the use of a HLA-mismatched unrelated donor
      (MMUD). HLA-mismatching is defined as the presence of unshared antigens/alleles in
      recipient-donor pairs for HLA-A, -B, -C or DRB1 loci.

      Patients undergoing MUD or MMUD transplants usually receive an intensified three-drug
      immunosuppressive regimen: anti-thymocyte globulin in addition to the standard platform of a
      calcineurine-inhibitor and an anti-metabolite.

      The effect of HLA mismatches on clinical outcomes has been investigated in several studies.
      Single HLA mismatches at HLA-A, -B, -C, or -DRB1 locus (7/8 HLA-matched) were associated with
      lower overall survival and disease free survival, higher non-relapse mortality, and higher
      incidence of acute GvHD as compared with 8/8 HLA-matched pairs.

      Many clinical trials suggest that high-dose Cy administrated after allogeneic HSCT didn't
      cause prolonged aplasia due toxicity on donor stem cells; could prevent rejection due to
      HLA-disparity and could be effective in preventing GvHD, allowing adequate
      immune-reconstitution.

      With this study the investigators plan to investigate if post-transplant high-dose Cy, with a
      calcineurine inhibitor and mycophenolate, could reduce acute GvHD rates and infectious
      complications improving clinical outcomes of MMUD transplants in patients with acute myeloid
      leukemia and myelodysplastic syndrome.
    

Intervention name(s): GvHD prophylaxis
Intervention type(s): Drug
Intervention description(s): Cyclophosphamide 50 mg/kg intravenously day+3 and +4 (total dose:100 mg/kg).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Allogeneic hematopoietic stem cell transplantation; acute graft-versus-host disease; Unrelated donors; Post-transplant cyclophosphamide; Myeloid Malignancies; unrelated hematopoietic cell transplantation; GITMO