Giving Chemotherapy for a Shortened Amount of Time Before a Stem Cell Transplantation

Inclusion Criteria:

- Patients aged ≥ 18 years old.

- Patients with any of the following hematologic malignancies for which allo-HCT is indicated, including:

- Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1.

- Relapsed AML in ≥ CR2.

- Acute leukemias of ambiguous lineage in ≥ CR1.

- Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR2.

- CML meeting one of the following criteria:

- Failed response to or intolerant to BCR-ABL tyrosine kinase inhibitors (TKIs).

- CML with BCR-ABL mutation consistent with poor response to TKIs (e.g., T315I mutation)

- CML in accelerated phase or blast crisis with <10% blasts after therapy, or in second chronic phase.

- Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN overlap syndromes with least one of the following:

- Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.

- Life-threatening cytopenias.

- Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.

- Therapy related disease or disease evolving from other malignant processes.

- Chronic myelomonocytic leukemia (CMML-1 or CMML-2).

- Severe aplastic anemia.

- Relapsed Hodgkin lymphoma meeting both of the following criteria:

- Responding to therapy prior to enrollment.

- Relapse after autologous HCT or are ineligible for autologous HCT.

- Relapsed non-Hodgkin lymphoma meeting both of the following criteria:

- Responding to therapy prior to enrollment.

- Relapse after prior autologous HCT or are ineligible for autologous HCT.

- High-risk multiple myeloma following autologous HCT or relapsed multiple myeloma following autologous HCT with chemosensitive disease.

- Adequate organ function is required, defined as follows:

- Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.

- AST, ALT, and alkaline phosphatase < 3 times the upper limit of normal unless thought to be disease-related.

- Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft Gault)

- LVEF ≥ 45% by MUGA or resting echocardiogram.

- Pulmonary function (FEV1 and corrected DLCO) ≥ 50% predicted.

- Adequate performance status of ECOG ≤ 2.

- Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

- Patients with active extramedullary disease.

- Patients with active central nervous system malignancy.

- Active and/or uncontrolled infection at the time of allo-HCT.

- Patients who have undergone previous allo-HCT.

- Patients who have undergone previous autologous HCT within the last 6 months, with the exclusion of high-risk multiple myeloma patients.

- Patient seropositivity for HIV I/II and/or HTLV I/II.

- Females who are pregnant or breastfeeding.

- Patients unwilling to use contraception during the study period.

- Patient or guardian unable to give informed consent or unable to comply with the treatment protocol.

Donor Inclusion and Exclusion Criteria:

- Must be a 10/10 HLA genotypically matched related or unrelated donor at A, B, C, DRB1, and DQB1 loci, as tested by DNA analysis.

- Able to provide informed consent for the donation process per institutional standards.

- Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines.