reduced intensity conditioning transplant using haploidentical donors

Conditions: Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myelofibrosis; CMML; Multiple Myeloma

Summary: 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

Keywords: cml aml mds all cll/cpl hd nhl mps cmml mm