Reduced Intensity Conditioning Transplant Using Haploidentical Donors

This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.

Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 \& 4 post-transplant.

Eligibility Criteria:
Inclusion Criteria:

* No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant
* Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)
* Karnofsky status ≥70%
* One of the following high-risk malignancies:

  1. Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy
  2. Acute Myelogenous Leukemia in first or greater remission
  3. Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of \<10%; CMML
  4. Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts \<5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
  5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
  6. Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
  7. Myeloproliferative diseases (myelofibrosis, CMML)
  8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors

Exclusion Criteria:

* not be excluded on basis of sex, racial, or ethnic backgrounds
* poor cardiac function: left ventricular ejection fraction \<40%
* poor pulmonary function: FEV1 and FVC \<50% predicted
* poor liver function: bilirubin \>2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
* poor renal function: Creatinine \>2.0mg/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
* prior allogeneic transplant
* women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
* any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up