Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide

This is an interventional treatment trial for Blood Stem Cell Transplant Failure focused on measuring Hematologic Neoplasms, Blood Disorders, Blood Cancer, Transplantation, Blood And Marrow, Acute myelogenous leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Aplastic anemia, Chronic myelogenous leukemia, Chronic lymphocytic leukemia, Myeloproliferative disease, Hodgkin's disease, Non-Hodgkin's lymphoma, Multiple myeloma, Cyclophosphamide, Fludarabine, Melphalan, Mesna, Rituximab, Tacrolimus, Prograf, Mycofenolate mofetil, MMF, CellCept, G-CSF, Filgrastim, Neupogen Read More

Inclusion Criteria:

1. Patients < 55 years (Myeloablative regimen #1) or > 55 and </= 75 years or significant comorbidities (Reduced intensity regimen #2) old lacking a matched related volunteer donor identified in time for transplant for which a related haploidentical donor (</= 7/8 allele match at the A, B, C, DR loci), a 7/8 allele matched related or unrelated donor is identified, or a matched unrelated donor (MUD). The patients must be diagnosed with a high-risk disease defined as following:
2. Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; ALL in second or greater remission or ALL with relapsed disease, peripheral blood blasts < 1000/microliter, ALL patients must show response to most recent received chemotherapy;
3. Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease or high-risk features defined as: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7 classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 [> 3 abnormalities], peripheral blood blasts <1000/microliter, AML patients must show response to most recent received chemotherapy;
4. AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts <1000/microliter; patients > 55 years and </= 75 years need to be in morphologic remission at transplant (< 5% blasts).
5. Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) intermediate-2 or higher; or therapy-related MDS
6. Aplastic anemia with Absolute neutrophil count (ANC)<1000 and transfusion dependent after they failed immunosuppression therapy
7. Chronic myeloid leukemia (CML) >/=1st chronic phase, after failed >/=2 lines of tyrosine kinase inhibitors; in accelerated or blast phase with > 30% bone marrow blasts;
8. Prior allogeneic stem cell transplant more than 6 months from the first transplant, in remission.
9. Chemotherapy-sensitive relapsed lymphoma (Complete or partial response), Hodgkin's or non-Hodgkin's lymphoma, no evidence of "bulky" disease (> 10 cm in diameter);
10. Patients with chemo-sensitive CLL with persistent or recurrent disease after fludarabine-based regimens, no evidence of "bulky" disease (> 10 cm in diameter)
11. Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p, t(1;14) or t(14;16) or hypodiploidy, with advanced disease (stage>/=2) and /or relapsed after autologous stem cell transplant.
12. Patients with myelofibrosis (Lille >0, transfusion dependency, progression to blast phase; however, in remission from AML) or chronic myelomonocytic leukemia (CMML). These patients will be treated with the reduced-intensity conditioning regimen #2 and will be subject to the same stopping rule as the group >/= 55 years or with comorbidities.
13. Zubrod performance status 0-1 or Lansky PS greater or equal to 70%.
14. Patients above >/=65 years old should have an age-adjusted co-morbidity index of </= 3.
15. Available donor able to undergo a bone marrow harvest. For matched unrelated donor transplants only: Peripheral blood stem cells may be collected if donor is unavailable for bone marrow harvest or if adequate bone marrow cannot be collected.
16. Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml.
17. Serum creatinine clearance >/=50 ml/min (calculated with Cockcroft-Gault formula); Creatinine for children </=1.5 mg/dl or </=2 times upper limit of normal for age (whichever is less);
18. Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function, >/= 92% oxygen saturation with pulse oximetry.
19. Left ventricular ejection fraction (LVEF) >/= 40%.
20. Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.

Exclusion Criteria:

1. HIV positive; active hepatitis B or C
2. Patients with active infections. The PI is the final arbiter of the eligibility.
3. Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
4. Uncontrolled central nervous system (CNS) involvement by tumor cells
5. Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts.
6. History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3-year limit: non-invasive nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.)
7. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
8. Inability to comply with medical therapy or follow-up.