Overview
Optimization of bendamustine-containg graft-versus-host disease (GVHD) prophylaxis to reduce the incidence of secondary haemophagocytic lymphohistiocytosis and GVHD
Description
Prognosis of patients undergoing allogeneic stem cell transplantation (HCT) for high-risk myeloid malignancies, including refractory acute myeloid leukemia, with standard HCT technologies have relatively poor prognosis with 10-30% long-term disease-free survival. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. The combination bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
Eligibility
Inclusion Criteria:
- Patients with indication for allogeneic hematopoietic stem cell transplantation
- Patients with \<10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Peripheral blood stem cells or bone marrow as a graft source
- Diagnosis:
Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: \>5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: \>5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable
\- No severe concurrent illness
Exclusion Criteria:
- Patients with indication for allogeneic hematopoietic stem cell transplantation
- Patients with \<10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Peripheral blood stem cells or bone marrow as a graft source
- Diagnosis:
Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: \>5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: \>5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable
\- No severe concurrent illness