Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms

Inclusion Criteria

INCLUSION CRITERIA (ENROLLMENT)

• Relapsed or refractory high-grade myeloid neoplasms, defined as having a blast count of >= 10% blasts at initial diagnosis; examples include excess blasts (EB)-2, with >= 10% blasts at initial diagnosis, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML-2); standard definitions of relapse will apply (i.e., characterized by >= 5% abnormal blasts or blast equivalents as assessed by multiparameter flow cytometry or morphologic examination; peripheral blood blasts or blast equivalents; or extramedullary granulocytic sarcoma, per European LeukemiaNet [ELN] 2017 guidelines); bone marrow aspirate/biopsy will be accepted if performed outside University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC); determination of disease status should occur within 30 days of signing informed consent
• R/R high-grade myeloid neoplasm following intensive induction chemotherapy; relapsed high-grade myeloid neoplasm: patients will be classified as relapsed if they have >= 5% blasts after being in a complete remission (CR) following treatment for high-grade myeloid neoplasm; refractory high-grade myeloid neoplasm: patients may be classified as refractory if they have received at least one prior cycle of induction chemotherapy, whether with cladribine cytarabine mitoxantrone (GCLAM) or another regimen

** Patients may have received up to two courses of intensive induction chemotherapy during initial treatment prior to enrollment on this protocol; for example, patients who have received two courses of granulocyte colony stimulating factor (G-CSF) GCLAM (or similar) chemotherapy, with most recent high-dose cytarabine-containing chemotherapy > 6 months ago and CR lasting > 6 months, will be eligible for this protocol; regimens "similar to GCLAM" would include cytarabine at doses of 1g/m^2 for at least 5 doses; examples of regimens "similar to GCLAM" would be GCLA, fludarabine cytarabine granulocyte (FLAG), and FLAG-idarubicin (ida); however, patients who received more than two courses of GCLAM (or similar) chemotherapy, or patients who received two courses of GCLAM and had CR lasting = 10% blasts will be eligible for the study (they will be considered refractory); similarly, patients who have received three or more cycles of HMA therapy who have had a response (e.g., achieving CR with 2 x upper limit of normal, unless these abnormalities are thought to be related to Gilbert's disease or leukemic infiltration of hepatic parenchyma

• Known human immunodeficiency virus (HIV) positivity
• Pregnant or nursing (to be confirmed with quantitative human chorionic gonadotropin [HCG] testing)
• Invasive solid tumor within 5 years; non-melanoma skin cancer or in situ malignancies are allowed
• Evidence of serious uncontrolled infection
• Eastern Cooperative Oncology Group (ECOG) of 3 or 4
• EXCLUSION CRITERIA (TRANSPLANT)
• Donor specific antibodies against donor HLA-DQ or -DP
• Active bacterial, fungal or viral infections unresponsive to medical therapy
• Active leukemia in the central nervous system (CNS)
• HIV positive
• Cardiac ejection fraction 2 x upper limit of normal, unless these abnormalities are thought to be related to Gilbert's disease or leukemic infiltration of hepatic parenchyma

DONOR SELECTION:

Identification of an appropriate donor will follow the general guidelines listed below.

• HLA-matched related or unrelated donor. Donors must be:
• Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
• Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
• HLA-mismatched unrelated donor. Unrelated volunteer donors who are mismatched with the recipient within one of the following limitations will be permitted:
• Mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele, but matched for HLA-DRB1 and HLA-DQ, OR
• Mismatched for two HLA class I alleles, but match