Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

Background: * Graft versus host disease (GVHD) and impaired immune reconstitution are major transplant complications and barriers to improving outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) for hematologic malignancies. GVHD is initiated when donor T-cells become alloreactive against recipient major or minor histocompatibility antigens. This process may be exacerbated during the transplantation process by exposure of tissue antigens to donor T-lymphocytes after chemotherapy-induced injury. * Palifermin, a recombinant keratinocyte growth factor-1 (KGF-1), imitates the actions of intrinsic KGF and binds to the Fibroblast growth factor (FGF) receptor 2b, which is expressed in the epidermis, oral mucosa, gastrointestinal (GI) mucosa and urothelium, thereby increasing the regenerative capacity of these tissues. Palifermin has been shown to reduce the duration and severity of oral mucositis after intensive chemo-radiotherapy and autologous HSCT for hematologic cancers and is Food and Drug Administration (FDA) approved. In pre-clinical studies, palifermin has been shown to have an effect on control of acute or chronic GVHD and immune reconstitution after alloHSCT. However, subsequent clinical studies in alloHSCT indicate that the dose and schedule of palifermin as currently used in humans does not optimize its activity in terms of prevention of GVHD or thymus recovery following alloHSCT. \- We hypothesize that higher doses of palifermin in the immediate pre alloHSCT conditioning setting will lead to enhanced thymopoiesis, decreased chronic GVHD, and improved immune reconstitution. A dose escalation study is necessary to determine safe dosing levels in persons undergoing alloHSCT. Objectives: * The primary objective of the phase I portion is to assess the safety and tolerability of the administration of the recombinant keratinocyte growth factor (KGF) palifermin in alloHSCT using unrelated donor peripheral blood stem cells. * The primary objective of the phase II portion is to determine the incidence of severe chronic GVHD after the addition of palifermin to TMS (tacrolimus, methotrexate and sirolimus) based GVHD prophylaxis delivered in the identical fashion to the NCI 07-C-0195 study. Eligibility: * Adults (greater than or equal to 18 years) with advanced or high-risk hematologic malignancies (including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), chronic myeloid leukemia (CML), multiple myeloma, and myeloproliferative neoplasm (MPN) who lack a suitable human leukocyte antigens (HLA)-matched sibling donor. * An unrelated donor matched at a minimum of 8 alleles (HLA-A,-B,-C, and major histocompatibility complex, class II, DR beta 1 (DRB1) by high-resolution typing, identified through the National Marrow Donor Program. * Karnofsky greater than or equal to 60 and acceptable organ functions. Design: * Patients will receive disease-specific induction chemotherapy etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride with fludarabine and rituximab (EPOCH-F/R or fludararbine, ara-c, granulocyte colony-stimulating factor (FLAG) prior to transplant as needed for disease control and immune depletion. * All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m\^2/day intravenous (IV) for 4 days and fludarabine 30 mg/m\^2/day for 4 days (transplant days -6 to -3). * All patients will receive a peripheral blood stem cell product from an unrelated donor matched at HLA-A, -B, -C, -DRB1 (8/8) by high-resolution typing. * Palifermin will be administered in a phase 1, open label design with the following proposed schedule: * Dose level 1: 180 mcg/kg on day -7 * Dose level 2: 360 mcg/kg on day -7 * Dose level 3: 540 mcg/kg on day -7 * Dose level 4: 720 mcg/kg on day -7 * The phase I portion will be conducted in a standard 3+3 design; the maximum possible number of patients accrued to this portion will be 24. * The maximum tolerated dose (MTD) from the phase I portion of the study will be used to conduct a phase II study. Total accrual on the phase II study will be 27 patients, including 3-6 patients treated at the MTD in the phase I portion of the study