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

The purpose of this study is to see if a condensed version of the chemotherapy regimen busulfan, melphalan, fludarabine (bu/mel/flu) and the drug antithymocyte globulin (ATG-also referred to as rATG or thymoglobulin) can have the same or fewer number of severe side effects in people with various blood cancers 30 days after they receive an allogeneic hematopoietic cell transplantation.


Eligibility Criteria:
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.