Reduced Intensity Conditioning and Stem Cell Transplant in Treating Patients with Blood Cancer

Inclusion Criteria

• Must have no 7/8 or 8/8 human leukocyte antigen (HLA)-matched sibling donor; we recommend counseling patients >= 65 about the higher risk of non-relapse mortality (NRM), especially in the context of co-morbidities
• Adequate performance status is defined as Karnofsky score >= 70% (> 16 years of age) or Lansky score >= 70 (pediatrics)
• Patients and selected donor must be HLA typed at high resolution using deoxyribonucleic acid (DNA) based typing at the following HLA-loci: HLA-A, -B, -C and DRB1; donors must be HLA-haploidentical relatives including, but not limited to, children, siblings, or parents, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1
• Acute leukemias: Must be in remission by morphology (< 5% blasts); NOTE: cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration versus (vs.) early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
• Acute myeloid leukemia (AML): second or greater complete remission (CR); first CR (CR1) in patients >= 60 years old; CR1 in < 60 years old that is NOT considered as favorable risk * Favorable risk AML is defined as having one of the following: * t(8,21) without cKIT mutation * inv(16) or t(16;16) without cKIT mutation * Normal karyotype with mutated NPM1 but FLT3-ITD wild type * Normal karyotype with double mutated CEBPA * Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
• Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following: * Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1 * Recipient age 30 years and older at diagnosis * White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis * Central nervous system (CNS) leukemia involvement during the course of disease * Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy) * Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
• Biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent CR
• Myelodysplastic syndrome: any subtype including refractory anemia (RA) if severe pancytopenia or complex cytogenetics; blasts must be less than 5%. If 5% or more requires chemotherapy for cytoreduction to =< 5% prior to transplantation
• Chronic myelogenous leukemia in chronic or accelerated phase; chronic phase patients must failed at least two different TKIs, been intolerant to all available TKIs or have T315I mutation
• MRD positive leukemia (AML, ALL or accelerated/blast phase chronic myelogenous leukemia [CML]); selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status
• Leukemia or myelodysplastic syndrome (MDS) in aplasia; these patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease >= 28 days post-therapy; these high risk patients will be analyzed separately
• Myeloproliferative neoplasms/myelofibrosis
• Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
• Burkitt’s lymphoma in CR2 or subsequent CR
• Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/partial response (PR) that has failed or ineligible for an autologous transplant
• Natural Killer cell malignancies
• Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of achieving a partial or complete remission; patients who had remissions lasting > 12 months, are eligible after at least two prior therapies; patients with bulky disease should be considered for debulking chemotherapy before transplant; patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month
• Lymphoplasmacytic lymphoma is eligible after initial therapy if chemotherapy sensitive
• Relapsed multiple myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
• Bone marrow failure syndromes, except for Fanconi anemia
• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction >= 40%; for children that are not able to cooperate with multi-gated acquisition (MUGA) and echocardiography, such should be clearly stated in the physician’s note
• Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume 1 (FEV1), forced vital capacity (FVC) > 40% predicted, and absence of oxygen (O2) requirements; for children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted; if nether test can be obtained it should be clearly stated in the provider’s note
• Transaminases < 5 x upper limit of normal (ULN) and total bilirubin =< 2.5 mg/dL except for patients with Gilbert’s syndrome or hemolysis
• Creatinine =< 2.0 mg/dL (adults) and creatinine clearance > 40 mL/min (pediatrics); adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min/1.73m^2
• Patients who are human immunodeficiency virus positive (HIV+) must have undetectable viral load; all HIV+ patients must be evaluated by infectious disease (ID) and a HIV management plan establish prior to transplantation
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
• Voluntary written consent (adult; legally authorized representative on behalf of cognitively impaired adult; or parent/guardian with presentation of the minor information sheet, if appropriate)

Exclusion Criteria

• =< 75 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
• Pregnant or breast feeding; the agents used in this study include pregnancy category D: known to cause harm to a fetus; females of childbearing potential must have a negative pregnancy test prior to starting therapy
• Current active and uncontrolled serious infection
• Less than 3 months since prior myeloablative transplant (if applicable); less than 6 months since prior autologous transplant (if applicable)
• Evidence of progressive disease by imaging modalities or biopsy - persistent positron emission tomography (PET) activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of computed tomography (CT) changes indicating progression
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy. Stable non-bulky disease is acceptable
• Active central nervous system malignancy