NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Fanconi Anemia; Aplastic Anemia
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Anemia; Myelodysplastic Syndromes; Anemia, Aplastic; Myeloproliferative Disorders; Fanconi Anemia; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: anti-thymocyte globulin; graft-versus-tumor induction therapy; sargramostim; therapeutic allogeneic lymphocytes; cyclophosphamide; fludarabine phosphate; methylprednisolone; mycophenolate mofetil; tacrolimus; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; umbilical cord blood transplantation
Intervention description: iv; iv; iv; iv; injection; iv; oral; oral; oral; iv; iv; iv
Intervention MeSH terms: Mycophenolic Acid; Methylprednisolone; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus; Antilymphocyte Serum; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 4 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: accelerated phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; primary myelofibrosis; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory anemia with excess blasts; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; Waldenstrom macroglobulinemia; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; childhood acute lymphoblastic leukemia in remission; adult acute lymphoblastic leukemia in remission; noncontiguous stage II adult lymphoblastic lymphoma; refractory multiple myeloma; refractory anemia; refractory chronic lymphocytic leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; grade 1 follicular lymphoma; grade 2 follicular lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell
      transplant helps stop the growth of cancer cells. It also stops the patient's immune system
      from rejecting the donor's stem cells. The donated stem cells may replace the patient's
      immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving
      an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help
      increase this effect. Sometimes the transplanted cells from a donor can also make an immune
      response against the body's normal cells. Giving immunosuppressive therapy before or after
      the transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral
      stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of aplastic anemia

               -  Severe disease

               -  Failed at least 1 course of standard immunosuppressive regimen with cyclosporine
                  and anti-thymocyte globulin OR

          -  Histologically confirmed hematologic malignancy including the following:

               -  Acute leukemia

                    -  Any of the following types:

                         -  Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes

                         -  Secondary AML

                         -  AML with high-risk cytogenetic abnormalities

                         -  Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities

                    -  Resistant or recurrent disease after combination chemotherapy with at least
                       1 standard regimen OR

                    -  In first remission at high risk of relapse

               -  Chronic myelogenous leukemia

                    -  Chronic phase meeting at least 1 of the following criteria:

                         -  Failed imatinib mesylate

                         -  Failed interferon after at least 6 months of treatment with minimum of
                            21 million units of interferon per week

                         -  Unable to tolerate interferon

                    -  Accelerated phase (blasts less than 20%)

               -  Myeloproliferative and myelodysplastic syndromes

                    -  Myelofibrosis (after splenectomy)

                    -  Refractory anemia

                    -  Refractory anemia with excess blasts

                    -  Chronic myelomonocytic leukemia

               -  Lymphoproliferative disease

                    -  Chronic lymphocytic leukemia

                         -  Symptomatic disease after first-line chemotherapy

                    -  Low-grade non-Hodgkin's lymphoma (recurrent or persistent)

                         -  Symptomatic disease after first-line chemotherapy

                    -  Multiple myeloma

                         -  Progressive disease after autologous stem cell transplantation

                    -  Waldenstrom's macroglobulinemia

                         -  Failed 1 standard regimen

               -  Non-Hodgkin's lymphoma meeting the following criteria:

                    -  Intermediate or high grade

                    -  Controlled and chemosensitive disease

                    -  First remission lymphoblastic or small non-cleaved cell lymphoma at high
                       risk of relapse

               -  Hodgkin's lymphoma

                    -  Relapsed and chemosensitive disease

          -  Not eligible for standard myeloablative allogeneic stem cell transplantation

          -  Availability of any of the following donor types:

               -  Related donor matched at 5 or 6 HLA antigens (A, B, DR)

               -  Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci

                    -  Single antigen mismatch at C allowed

               -  Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE:
                  No syngeneic donors permitted

          -  No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification
             scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of
             "indolent" or "aggressive" lymphoma will replace the former terminology of "low",
             "intermediate", or "high" grade lymphoma. However, this protocol uses the former
             terminology.

        PATIENT CHARACTERISTICS:

        Age

          -  4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation)

          -  4 to 60 (if unrelated cord blood transplantation)

        Performance status

          -  Karnofsky > 50%

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Not specified

        Hepatic

          -  Bilirubin less than 3 times normal

          -  Alkaline phosphatase less than 3 times normal

          -  AST/ALT less than 3 times normal

          -  No Child's class B or C liver failure

        Renal

          -  Creatinine clearance greater than 40 mL/min

        Cardiovascular

          -  Cardiac ventricular ejection fraction at least 35% by MUGA

          -  No cardiovascular disease

        Pulmonary

          -  DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  HIV antibody negative

          -  No uncontrolled diabetes mellitus

          -  No active serious infection

          -  No other disease that would preclude study therapy

          -  No other concurrent malignancy except non-melanoma skin cancer

          -  No concurrent serious psychiatric illness

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  See Disease Characteristics

          -  patients may have received a prior autologous blood or marrow transplantation (BMT)

          -  At least 6 months since prior allogeneic BMT

        Chemotherapy

          -  See Disease Characteristics

          -  At least 2 weeks since prior chemotherapy, radiation or surgery

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  At least 2 weeks since prior radiotherapy

        Surgery

          -  At least 2 weeks since prior surgery