Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug
(an immunosuppressant) given after transplant to help prevent certain complications, can be
given safely for a shorter period of time than it has been in the past. The experiences with
immunosuppression duration with other allogeneic HSCT platforms cannot be directly
extrapolated to the high-dose posttransplantation cyclophosphamide platform (another type of
immunosuppressant given after transplant to help prevent GVHD). There are presently no
published data on the minimum required duration of tacrolimus after nonmyeloablative HSCT
that includes high-dose Cy as part of postgrafting immunosuppression. The effectiveness of
high-dose posttransplantation Cy in GVHD prevention, however, permits the investigation of
this question. At the present time there are few or no cures for diseases studied on this
trial outside of a bone marrow or peripheral blood transplant. The peripheral blood for this
transplant comes from a relative who is a half-match or "haplo" match to the participant.
Possible donors include parents, siblings, and children. In order to help the bone marrow
grow, or "take", inside the body, participants will receive chemotherapy and radiation before
the transplant. After the transplant participants will receive high doses of cyclophosphamide
(Cytoxan®) along with other medications to lower the immune system, such as tacrolimus. These
medications may lower the risk of graft versus host disease (GVHD) and of rejection of the
peripheral blood graft.

Inclusion Criteria:

- Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a
10/10 matched unrelated donor

- Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature;
small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p
deletion or with progression < 6 months after a second or greater treatment regimen;
T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or
tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or
subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative
disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial
response or better; Hematologic malignancy in complete remission with minimal residual
disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or
molecular testing

- Any previous autologous transplant must have occurred > 3 months ago

- Left ventricular ejection fraction (LVEF) >= 35%, or shortening fraction > 25%

- Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis)

- AST and ALT <= 5 x institutional upper limit of normal

- FEV1 and FVC >= 40% of predicted; if unable to perform pulmonary function testing,
oxygen saturation > 92% on room air

- ECOG performance status <= 2, or Karnofsky/Lansky status >= 60

Exclusion Criteria:

- Pregnancy or active breastfeeding

- Uncontrolled active infection

- Previous allogeneic transplant

- Active extramedullary leukemia or active central nervous system (CNS) malignant
disease