Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Inclusion Criteria

• Diagnosis of a histology documented hematologic malignancy or marrow disorder
• Bone marrow failure disorders and other non-malignant hematologic or immunologic disorders:
• Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):
• Primary allogeneic hematopoietic stem cell transplantation (HSCT) is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available
• Patients with PNH must have a history of thrombosis related to PNH
• Hereditary bone marrow failure disorders include Fanconi anemia or related chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia:
• Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable
• Dyskeratosis: diagnosis is supported by using either telomerase reverse transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked DKC1 gene mutation
• Other non-malignant hematologic or immunologic disorders that require transplantation
• Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia)
• Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)
• Congenital primary immunodeficiencies (including but not limited to Severe Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand deficiency, T-cell deficiencies)
• Acute leukemias:
• Subjects must be ineligible for conventional myeloablative transplantation;
• Resistant or recurrent disease after at least one standard combination chemotherapy regime or first remission patients at high risk of relapse OR First remission patients at high risk of relapse:
• Acute myeloid leukemia (AML)- antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular features (e.g. Flt3-ITD mutation, mixed-lineage leukemia [MLL], wildtype NPM1);
• Acute lymphocytic leukemia (ALL)- high or standard risk ALL
• Chronic Myeloid Leukemia (CML):
• Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation
• Myeloproliferative and myelodysplastic syndromes (MDS):
• Myelofibrosis (with/without splenectomy) with intermediate to high risk features
• Advanced polycythemia vera not responding to standard therapy
• MDS with an international prostate symptom score (IPSS) score of Int-2 or higher
• MDS with lower IPSS scores Int-1 or less with severe clinical features such as severe neutropenia or thrombocytopenia or high risk chromosome abnormalities such as monosomy 7
• Secondary massively parallel signature sequencing (MPSS) with any IPSS scores
• Chronic myelomoncytic leukemia
• Lymphoproliferative disease:
• Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) fludarabine refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy
• Multiple myeloma, progressive disease after autologous stem cell transplant or as planned tandem (allogeneic transplant after prior autologous stem cell transplant)
• Waldenstroms macroglobulinemia (failed one standard regimen)
• High grade NHL and diffuse large B-cell lymphoma (DLBCL)
• Not eligible for conventional myeloablative HSCT OR failed autologous HSCT
• First remission lymphoblastic lymphoma, or s