In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.

Historically, haploidentical HSCT has been associated with significant risks of graft rejection and severe graft versus host disease (GVHD), leading to high treatment related mortality and poor outcomes. The risk of engraftment failure and GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Recently, investigators from Johns Hopkins University demonstrated a new approach to haploidentical transplantation, utilizing a nonmyeloablative preparative regimen, followed by a T cell-replete bone marrow infusion and post-transplantation immunosuppression with high dose Cyclophosphamide (Cy), tacrolimus, and MMF. Clinical studies have shown this approach to be safe and effective with a low incidence of graft rejection, GVHD, and treatment-related mortality. Relapse represents the major cause of treatment failure in these patients, particularly with high-risk myeloid malignancies.

In order to decrease this relapse risk in high-risk patients, the investigators initiated a myeloablative haploidentical HSCT study in January 2009 utilizing Busulfan-based conditioning, post-transplant Cy, and PBSC, instead of BM, as the stem cell source. Outcomes of the 15 patients transplanted to date have been promising with 100% engraftment, low rates of treatment-related mortality, relapse and GVHD, and excellent survival rates. An unexpected outcome of the study was a higher-than-expected rate of BK virus-induced hemorrhagic cystitis (HC) occurring in 7 of 14 evaluable patients. Although there were no deaths attributable to HC, it was associated with significant morbidity in some patients.

HC is a recognized complication of allogeneic transplant therapy. Late onset HC, occurring after engraftment, is due almost exclusively to reactivation of the polyoma BK virus (BKV). Other important risk factors associated with HC include Busulfan-based conditioning, acute GVHD, HLA mismatched transplants, and use of bone marrow as the stem cell source. TBI-based conditioning, prior to myeloablative allogeneic transplant, has been associated with significantly less HC than Busulfan-based conditioning in both retrospective and prospective randomized trials.

Eighteen patients will be accrued to this study. The primary end point of this study is the incidence of HC. The investigators will also examine the incidence of acute and chronic GVHD, engraftment, degree of donor-host chimerism, transplant related morbidity and mortality, as well as disease-free and overall survival. Stopping rules will minimize the risk of untoward or unexpected side effects.

Inclusion Criteria:

• No available matched related or unrelated donor OR a matched related or unrelated donor that is unavailable in the time frame necessary
• Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor
• Donor must have a negative HLA cross-match in the host vs. graft direction
• Donor must be willing to donate mobilized peripheral blood stem cells
• Age 18 to </=60 years
• Karnofsky Status >/= 70%
• Must have one of the following high-risk malignancies
• Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to TKI
• CML in accelerated phase
• CML blast crisis that has entered into 2nd Chronic phase following induction
• Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR)
• AML primary induction failure but subsequently in CR
• AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic disease
• AML with marrow blasts <5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH
• Myelodysplastic Syndrome (MDS) that is treatment related
• MDS that has monosomy 7 or complex cytogenetics
• MDS with IPSS score of 1.5 or greater
• Chronic myelomonocytic leukemia (CMML)
• Acute Lymphocytic Leukemia/lymphoblastic lymphoma (ALL) in 2nd or subsequent complete remission (CR)
• ALL with poor-risk karyotype [t(9;22) or bcr-abl fusion, t(4;11) or other MLL translocation] and in 1st CR
• ALL with marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH
• Chronic Lymphocytic Leukemia (CLL)/Prolymphocytic Leukemia (PLL) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
• Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
• Advance Myelofibrosis, Primary or Post-Polycythemia Vera/Essential Thrombocythemia. Patients must have one of more of the following accelerate phase features, which have been associated with a median overall survival of </= 15 months
• Blood or bone marrow blasts >/= 10%
• Platelets < 50 x 10*9/L
• Chromosome 17 aberrations

Exclusion Criteria:

• Patients will not be excluded on the basis of sex, racial or ethnic background
• Poor cardiac function: Left ventricular ejection fraction < 45%
• Poor pulmonary function: FEV1 and FVD < 60% predicted
• Poor liver function: bilirubin >/= 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT > 3x ULN
• Poor renal function: Creatinine >/= 2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum creatinine (mg/dl)
• HIV positive
• Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.
• Prior irradiation therapy rendering patient ineligible for TBI