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 \< 6 months, would not be eligible
  * R/R high-grade myeloid neoplasm following less intensive induction chemotherapy. Patients who have received at least three cycles of treatment with a hypomethylating agent (HMA; such as azacitidine or decitabine) and still have \>= 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 \< 5% blasts), but who then progress using standard definitions of relapse, will also be eligible (they will be considered relapsed)
* Potentially eligible for reduced intensity conditioning based on known organ function (formal organ function testing may occur after consent)
* Caregiver capable of providing post-HCT care
* Written informed consent

INCLUSION CRITERIA (TRANSPLANT)

* Identified donor (see DONOR SELECTION below for further details)

  * Matched related or unrelated (one allele mismatch in HLA-A, B, or C OK) donor according to institutional standards
  * Unrelated volunteer donor who is mismatched with the recipient (i.e. 9/10 match)
* Caregiver capable of providing post-HCT care, who will be present once induction therapy with filgrastim, cladribine, cytarabine, mitoxantrone hydrochloride (GCLAM) begins
* Written informed consent for transplant
* Either bone marrow or peripheral blood is allowed

Exclusion Criteria:

EXCLUSION CRITERIA (ENROLLMENT)

* Prior allogeneic HCT
* More than two prior courses of induction chemotherapy
* Relapse after minimal residual disease (MRD)-negative CR within 3 months of most recent GCLAM chemotherapy
* Low likelihood of being eligible for reduced intensity conditioning HCT based on known information

  * Cardiac ejection fraction \< 40% or symptomatic coronary artery disease or uncontrolled arrhythmia, as assessed by multigated acquisition (MUGA) or transthoracic echocardiography (TTE) within previous 3 months and since the most recent anthracycline exposure
  * Corrected diffusing capacity of the lungs for carbon monoxide (DLCOc) \< 40% or forced expiratory volume in 1 second (FEV1) \< 50%
  * Estimated glomerular filtration rate (GFR) \< 40 ml/min
  * Need for supplemental oxygen
  * Direct bilirubin or alanine aminotransferase (ALT) \> 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 \< 40% or symptomatic coronary artery disease or uncontrolled arrhythmia
* DLCOc \< 40% or FEV1 \< 50%
* Estimated GFR \< 40 ml/min
* Need for supplemental oxygen
* Direct bilirubin or ALT \> 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 matched for HLA-DRB1 and HLA-DQ
  * HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch

HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQ. If the patient is homozygous at the mismatch HLA class I locus or II locus, the donor must be heterozygous at that locus and one allele must match the patient (i.e., patient is homozygous A\*01:01 and donor is heterozygous A\*01:01, A\*02:01)