Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies

Inclusion Criteria

• Acute leukemia (AL) that includes acute myeloid leukemia (AML) / acute lymphoblastic leukemia (ALL) / mixed phenotype leukemia (MPAL) in complete morphological remission (CR) with or without detectable minimal residual disease (MRD); complete morphological remission is defined by the presence of less than 5% of detectable blasts in bone marrow specimen, evaluated per standard of care. Patients with documented CR but without hematologic recovery since last chemotherapy are considered eligible to the study
• Chronic myelogenous leukemia (CML), except refractory blast crisis. To be eligible in first chronic phase, patients must have failed or be intolerant to at least one tyrosine-kinase inhibitor
• Chronic myelomonocytic leukemia (CMML)
• Myelodysplastic syndromes (MDS)
• Lymphoblastic, Burkitt's and other high-grade lymphoma in any complete (CR) or partial (PR) response

• CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• Low grade lymphoma (chronic lymphocytic leukemia [CLL]/small lymphocytic lymphoma [SLL], marginal zone lymphoma, follicular lymphoma) progressed after two treatment regimens, in CR/PR

• For CLL/SLL, CR and PR are defined according to: International Workshop on CLL (iwCLL) guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
• CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• Large cell lymphoma in > second CR (CR2)/ >= PR2

• CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• Mantle cell lymphoma, lymphoplasmacytic lymphoma and prolymphocytic leukemia may be eligible after initial therapy if in CR/PR

• CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• For prolymphocytic leukemia (PLL), CR is defined as a normalization of lymphadenopathies (long-axis diameter \< 1 cm) and splenomegaly (\< 13 cm), absence of constitutional symptoms, PLL cells \< 5% in bone marrow and circulating lymphocytes count \< 4 x 10\^9/L. Patients without hematopoietic recovery are considered eligible to the study. PR is defined as a decrease of >= 30% of the sum of lymphadenopathies' long-axis diameters, a decrease of >= 50% in spleen vertical length beyond normal from baseline, peripheral blood (PB) lymphocytes =\< 30 x 10\^9/L (and a decrease of >= 50% from baseline)
• Hodgkin Lymphoma in > CR2/PR2

• CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• Subjects must be >= 6 months old
• Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 (for adults)
• Lansky score >= 50 (for children)
• Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 40% or shortening fraction > 22%
• Adequate pulmonary function defined as absence of oxygen (O2) requirements and one of the following:

• Diffusion capacity of the lung for carbon monoxide (DLCO) corrected >= 70% mm Hg
• DLCO corrected between 60% - 69% mm Hg and partial pressure of oxygen (pO2) >= 70 mm Hg
• DLCO corrected between 50% - 59% mm Hg and pO2 >= 80 mm Hg Pediatric patients unable to perform pulmonary function tests must have O2 saturation >= 92% on room air. May not be on supplemental oxygen
• Total bilirubin \< 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Alkaline phosphatase =\< 5 x ULN
• Creatinine \< 2.0 mg/dl (adults) or estimated creatinine clearance > 40 ml/min (pediatrics)

• All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
• If recent mold infection, e.g., aspergillus, must be cleared by infectious disease to proceed
• Patients who have undergone prior allogeneic hematopoietic cell transplant are eligible, but the prior transplant must have been performed at least 3 months prior to enrollment, unless in case of graft failure from the prior transplant
• Written and signed informed consent
• DONOR: Donors must be haploidentical relatives of the patients. Donor-recipient compatibility will be tested through HLA typing at high resolution for the HLA loci (-A, -B, -C, -DRB1, -DQB1). Donor and recipient should share at least 5/10 HLA loci
• DONOR: Age >= 12 years
• DONOR: Weight >= 40 Kg
• DONOR: Ability of donors younger than 18 years of age to undergo apheresis without use of a vascular access device. Vein check must be performed and verified by an apheresis nurse prior to arrival.
• DONOR: Donor must meet selection criteria as defined by the Foundation of the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines
• DONOR: In case of more available haploidentical donors, selection criteria should include, in this order:

• For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
• Red blood cell compatibility

• Red blood cell (RBC) cross match compatible
• Minor ABO incompatibility
• Major ABO incompatibility

Exclusion Criteria

• Active, uncontrolled, life-threatening viral, bacterial or fungal infection requiring treatment at time of conditioning regiment administration and transplantation
• Presence of a malignancy other than the one for which the transplant is being performed, with an expected survival less than 75% at 5 years
• Pregnant or breastfeeding
• Known hypersensitivity to treosulfan, fludarabine or cyclophosphamide
• Dosing with another investigational agent within 30 days prior to entry in the study
• Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning (day -6)
• DONOR: Since detection of anti-donor-specific-antigen antibodies (anti-DSA) is associated with higher graft rejection rate, patients will be screened for anti-DSA pre-transplant. Patients with DSA mean fluorescent intensity (MFI) \< 5000 after desensitization treatment, will be considered eligible to participate in the study. The first 10 subjects enrolled in the trial will be DSA-negative.