Trial Information

Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Hematologic Malignancies

PATIENT ENROLMENT.

It is expected that about 15 patients / year will be enrolled in this phase I-II protocol.
Patient selection will be based on the following criteria:

Eligibility Criteria:

1. Any patient with one of the following lympho or myeloproliferative malignancies or
syndromes in whom allogeneic NST is warranted. Patients with other selected
malignancies/disorders may also be considered but must be approved by the transplant
team and the Principal Investigator.

2. Patient age > 50 years, or for patients <50 years of age but because of pre-existing
medical conditions or prior therapy are considered to be at high risk for
regimen-related toxicity associated with conventional myeloablative transplants.

3. an HLA-identical sibling or matched unrelated donor is available. Patients with one
antigen mismatched donors can be considered but only after discussion with the
transplant team and the Principal Investigator.

STEM CELL TRANSPLANTATION:

(A) TLI Administration: see "brief description" (B) ATG: Thymoglobulin will be administered
five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of
7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight.
Premedication for thymoglobulin will include solumedrol 1.0 mg/kg.

Mobilized PBPC: The minimum cell doses (based on recipient body weight) for transplants are
> 5x106 CD34+ cells/kg. Cells collected on days -1 and 0 will be pooled and processed for
infusion on day 0. Fresh cells (not frozen) are to be infused. For related donor
transplants, if the target cell dose is not achieved then a third apheresis procedure may be
performed on day+1 and the cells infused on the same day. Collection of cells for unrelated
donor transplants will be coordinated through the Italian bone Marrow Transplant Registry
and subject to the rules of that Program. If mobilized PBPC is not available through certain
collection centers then bone marrow will be used.

(F) Cyclosporine (CSP): CSP is given at 6.25 mg/kg p.o. b.i.d (9 a.m and 9 p.m.) from day -3
until after the day +56 chimerism results are obtained. CSP will be tapered after the day
+56 chimerism results are obtained. If the day +56 chimerism results show >40% donor cells
in the CD3+ lineage, and the patient is without evidence of GVHD then CSP taper will begin.
The CSP will be tapered at 6% every week. Modifications of the taper schedule may be
indicated if significant disease progression occurs early post-transplantation or the
patient develops GVHD.

(G) Mycophenylate mofetil (MMF): Administration of MMF will begin at 15 mg/kg po on day 0,
at 5-10 hours after mobilized PBPC infusion is complete. Thereafter,beginning on day +1 MMF
is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related
donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched
donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be
stopped on day +28 for matched related donors and for one antigen mismatched or unrelated
donors beginning day +40 MMF will be tapered by 10% weekly till off, typically by day +96.

POST-TRANSPLANT FOLLOW-UP

Clinical: The incidence, severity and extent of acute and chronic GVHD will be monitored and
scored according to standard criteria. As well, documented and presumed post-transplant
infectious complications, rate of relapse, event-free and overall survival and transplant
related mortality will be recorded.

Assessment of Disease Response: Since the diseases treated on this protocol are
heterogenous, appropriate disease specific studies will be performed to evaluate response to
transplant. Responses will be classified as continued complete remission (CCR), achieved
complete remission (CRa), partial response (PR), progressive disease (PD), or no response
(NR). Disease response will be according to accepted criteria. All cases of progressive
disease should be discussed with the Principal Investigators. If patients show evidence of
progressive disease then they may be candidates for donor lymphocyte infusion.