Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Not Applicable

Completed

Conditions: Hodgkin's Disease
Acute Myeloid Leukemia
Chronic Myelogenous Leukemia
Myeloproliferative Disorder
Acute Leukemia
Lymphocytic Leukemia
Myelofibrosis
Malignant Lymphoma
Multiple Myeloma
Polycythemia Vera

Interventions: Drug: fludarabine/ melphalan
Drug: fludarabine/busulfan
Drug: ATG

Brief Summary: New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.

Detailed Description: Treatment-related mortality and recurrence of disease account for the majority of treatment failures in allogeneic transplantation for advanced hematologic malignancies. The most commonly utilized conditioning regimens consist of cyclophosphamide and total-body irradiation or busulfan and cyclophosphamide. Other agents such as etoposide or thiotepa are sometimes added to maximize the antileukemic effect. New conditioning regimens are however still needed to maximize efficacy and limit treatment-related deaths. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.

Recruitment & Eligibility

Inclusion Criteria

Patients with the following diseases:
- Acute myeloid or lymphocytic leukemia in first remission at standard or high-risk for recurrence.
- Acute leukemia in greater than or equal to second remission, or with early relapse, or partial remission.
- Chronic myelogenous leukemia in accelerated phase or blast-crisis.
- Chronic myelogenous leukemia in chronic phase
- Recurrent or refractory malignant lymphoma or Hodgkin's disease
- Multiple myeloma.
- Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
- Myeloproliferative disorder (polycythemia vera, myelofibrosis) with poor prognostic features.
- Severe aplastic anemia after failure of immunosuppressive therapy.
Age 10-65 years.
Zubrod performance status less than or equal to 2.
Adequate cardiac and pulmonary function. Patients with decreased LVEF < 40% or DLCO < 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol.
Patient or guardian able to sign informed consent.

Exclusion Criteria

Life expectancy is severely limited by concomitant illness.
Serum creatinine greater than 1.5 mg/dL or Creatinine Clearance less than 50 ml/min .
Serum bilirubin greater than or equal to 2.0 mg/dl, SGPT greater than 3 x upper limit of normal
Evidence of chronic active hepatitis or cirrhosis
HIV-positive
Patient is pregnant

Arm && Interventions

Group	Intervention	Description
Arm 2	fludarabine/ melphalan	All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Arm 1	fludarabine/busulfan	All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Arm 1	ATG	All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Arm 2	ATG	All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Engraftment.	Up to 30 days post-transplant	Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.

Secondary Outcome Measures

Name	Time	Method
Participants With 100 Day Transplant-related Mortality.	Up to 100 days post-transplant.	Day 100 transplant-related mortality was measured in both groups.
Time to ANC and Platelet Engraftment	Up to 30 days post-transplant	Days to ANC or platelet engraftment
Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).	Up to 100 days post-transplant (acute GVHD).	Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.