Stem cell transplantation is used to treat may types of diseases. There a 2 types of transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called mini-transplants.

This study proposes to use a conditioning regimen for allogeneic transplantation along with a reduced intensity transplant. Conditioning regiment is the name for the combination of chemotherapy drugs that is given to patients before receiving a transplantation of donor stem cells. It is hoped that the regimen designed for this study proves to be less toxic and has an equal or better anticancer effect than the regimens that are normally used. The regimen being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This regimen has been studied in recipients of matched sibling transplants and in recipients of alternative donor stem cells in other hematologic malignancies. Those subjects, who receive stem cells from an unrelated donor, will also receive and additional drug called ATG or anti thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the recipient rejecting the transplant (graft).

The purpose of this study is to observe if reduced intensity transplants can be used to allow engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this type of transplant is much less toxic than traditional bone marrow transplants. Reduced intensity transplants may be better tolerated by patients who may experience serious side effects from standard (very intense) stem cell transplant.

The study has been recently amended to follow all subjects for survival.

This study is designed as a single arm Phase II clinical trial in patients with myelofibrosis who are eligible for transplantation from a related donor or from an unrelated donor source. Patients will be accrued into two separate strata defined by donor type. Each of the two strata will be analyzed separately.

Patients will be followed yearly from time of enrollment into the study to assess clinical response and overall, progression and event free survival, as well as incidence and degree of acute and chronic GVHD. We will estimate cumulative survival and transplant related mortality in patients enrolled in each of the two strata.

Inclusion Criteria:

• Patients with the following disease: Idiopathic myelofibrosis, or spent PV-, or ET-related myelofibrosis in chronic phase (<20% blast cells in the bone marrow) with Lille score >1 at any time, or platelet <100K.
• Age 18-65 years.
• ECOG performance status < 3.
• Life expectancy >3 months.
• Adequate cardiac function, normal LVEF ≥ 45% by MUGA or echocardiogram and adequate pulmonary function DLCO ≥ 50% of predicted.
• Serum creatinine < 1.1 x the upper limit of normal (ULN) or Creatinine Clearance >50 ml/min.
• Serum bilirubin < 2.0 mg/dl, SGPT <2.5 x upper limit of normal
• No evidence of chronic active hepatitis or cirrhosis
• HIV-negative
• Patient is not pregnant
• Patient or guardian able to sign informed consent.
• Patients with >20% myeloblasts in the blood or marrow, extramedullary blast cell proliferation or large foci of blasts in bone marrow biopsy specimens are not eligible.
• Pretransplant splenectomy: MMM patients with variable degrees of splenomegaly, or splenectomized, are eligible to be enrolled. Any decision of having a patient splenectomized prior to transplant will be made in each center prior to enrolling the patient in the study.
• Patients should be off treatment with investigational for at least 4 weeks and have recovered from all toxicities.

Exclusion Criteria:

• Pregnancy
• HIV positive
• > 20% myeloblasts in the peripheral blood or bone marrow
• LVEF < 45%
• DLCO < 50% of predicted
• ECOG performance status ≥ 3
• Chronic active hepatitis or cirrhosis
• Chronic renal insufficiency