OBJECTIVES:

Primary

- Determine overall survival (OS) of patients with germ cell tumors treated with tandem autologous stem cell transplantation with non-cross-resistant conditioning regimens.

Secondary

- Determine disease-free survival (DFS) of patients treated with this regimen.

- Determine the toxicity of tandem transplants

- Determine the time to engraftment of neutrophils and platelets in patients treated for each transplant

- Determine the number of patients unable to adequately mobilize sufficient peripheral blood stem cells (PBSC) for tandem transplantation.

- Identify prognostic factors of patients unlikely to mobilize sufficient PBSC for tandem transplantation.

- Compare OS and DFS of patients undergoing single vs tandem transplantation.

OUTLINE:

- Peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF): Patients receive G-CSF subcutaneously (SC) beginning on day 1 and continuing until stem cell collection is complete. Patients undergo stem cell collection beginning on day 5 of G-CSF administration and continuing for at least 3 collections until the collection goal is met.

- Second PBSC mobilization with chemotherapy: Patients not meeting the collection goal receive cyclophosphamide IV over 2 hours on day 1 and G-CSF SC beginning on day 4 and continuing until stem cell collection is complete. Patients meeting the collection goal after PBSC mobilization via G-CSF alone or in combination with chemotherapy will undergo tandem autologous transplantation. If collection goal is not met but the patient has collected>> or = 2 x 10^6 CD34 cells/kg, a single autologous transplant will be performed.

- Single stem cell transplantation (SCT): Patients receive paclitaxel IV over 3 hours on day -7 and ifosfamide IV on days -6 to -4. Patients undergo reinfusion of stem cells on day 0. Patients also receive G-CSF SC or IV beginning on day 1 and continuing until blood counts recover.

- Tandem SCT: Patients receive treatment as in single SCT. Beginning 30-90 days later, patients receive carboplatin IV over 60 minutes and thiotepa IV over 30 minutes on days -6 to -4 and etoposide IV over 60 minutes on days -6 to -3. Patients undergo reinfusion of stem cells on day 0. Patients also receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed at 6, 9, and 12 months and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Background:

- In CC# 00-C-0119 we were able to demonstrate that allogeneic T cells could mediate a clinically relevant graft-versus-tumor (GVT) effect against MBC after a reduced-intensity, T cell depleted allogeneic hematopoietic stem cell transplant (alloHSCT).

- Responses were observed after establishment of complete lymphoid chimerism, which was frequently delayed and required the use of planned donor lymphocyte infusions (DLI). DLI were associated with a significant incidence of graft-versus-host disease (GVHD).

- In murine models, in vitro generated T cells of Th2/Tc2 phenotype can facilitate engraftment of HLA disparate allografts with significantly reduced GVHD as compared to T cell replete allografts that have not been manipulated. In addition, Th2/Tc2 cells provide an anti-tumor effect through the perforin/granzyme pathway.

- Allogeneic Th2/Tc2 cells may facilitate rapid allo-engraftment post-transplant with reduced GVHD. In addition, the perforin-mediated anti-tumor activity of Th2/Tc2 cells should provide earlier benefit compared with T-cell depleted allografts.

Objectives:

-To determine the safety, as defined by the incidence of acute graft-versus-host disease, and feasibility of administering in vitro generated donor T cells of Th2/Tc2 phenotype to augment a T cell depleted allograft (T cell exchange) after reduced-intensity conditioning.

Eligibility:

- Patients with measurable, metastatic breast cancer and an HLA matched sibling donor

- Patients must have received treatment with a taxane, an anthracycline, a hormonal agent and/or Herceptin, if the tumor expresses the respective receptors, and at least one treatment for metastatic disease that has not resulted in a complete response.

Design:

- Donors will initially have lymphocytes collected to generate the Th2/Tc2 product and then have blood stem cells collected following mobilization with filgrastim. The stem cell product will be T-cell depleted, and the T-cell dose will be adjusted to 1 x 10(5) CD3+ cells/kg.

- Patients will receive induction (immune depleting) chemotherapy with the goal of reducing circulating CD4+ cell less than 50/microliter prior to proceeding to alloHSCT.

- Patients will receive a reduced-intensity conditioning regimen consisting of fludarabine and cyclophosphamide. This will be followed by infusion of the T cell depleted allograft, which will be supplemented with Th2/Tc2 cells (i.e. T cell exchange).

- Cyclosporine will be discontinued after 40 days to permit a full GVT effect. Patients may receive donor lymphocyte infusions at days +42, +70, +98 post-transplant to further potentiate a GVT effect.

- Patients will be enrolled in three cohorts, with escalating Th2/Tc2 cell doses (0.5 - 12.5 x 10(7) cells/kg) given in a phase-I manner.

PRIMARY OBJECTIVE:

I. To evaluate the safety of tagraxofusp-erzs (tagraxofusp) in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) after autologous (auto) or allogeneic (allo) hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) in patients with BPDCN receiving maintenance therapy with tagraxofusp after auto-HCT or allo-HCT.

II. To estimate the overall survival (OS) in patients with BPDCN receiving maintenance therapy with tagraxofusp after auto-HCT or allo-HCT.

OUTLINE:

Within day 45 and 120 after stem cell transplant, patients receive tagraxofusp-erzs intravenously (IV) over 15 minutes on days 1-3 of cycles 1-4 and days 1-2 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 1 year.

OBJECTIVES:

- Determine the efficacy and safety of allogeneic peripheral blood stem cell transplantation in achieving engraftment in patients with hematologic malignancy.

- Determine the hematopoietic recovery, incidence of chemoradiotherapeutic toxicity, relapse, graft-versus-host disease, and survival of patients treated with this regimen.

OUTLINE: Patients receive a preparative chemoradiotherapeutic regimen and graft-versus-host disease prophylaxis prior to transplantation. Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

Patients are followed every 1-2 weeks for 6 months and at 9, 12, 24, and 36 months.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study within 4 years.

OBJECTIVES:

- Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.

- Determine the toxicity of this regimen in these patients.

- Determine the relapse rate and survival rate in patients treated with this regimen.

- Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.

OUTLINE: Patients receive 1 of the following preparative regimens:

- Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.

- Regimen B-1: Patients receive cyclophosphamide IV and TBI as in regimen A.

- Regimen B-2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.

- Regimen B-3: Patients receive TBI on days -7 to -5. Patients receive cyclophosphamide IV over on days -4 to -3.

- Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.

- Regimen D: Patients receive TBI on days -6 to -4. Patients receive etoposide infusion on day -3.

All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.

Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: 50

OBJECTIVES:

- Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.

- Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.

- Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.

- Determine the distribution of time-to-progression in patients responding to this regimen.

- Determine the percent donor chimerism in patients treated with this regimen.

- Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.

- Determine the toxic effects of this regimen in these patients.

- Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

- Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.

- Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease

- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.

- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

OBJECTIVES:

- Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with metastatic renal cell carcinoma.

- Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative regimen followed by an HLA-matched allogeneic PBSCT in these patients.

- Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid lineages in patients treated with this regimen.

- Determine the relationship between donor-host chimerism and the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.

- Determine the effect of lymphocyte infusions on donor-host chimerism in this patient population.

- Determine the response rate, disease-free survival, overall survival, and mortality from the procedure or tumor progression in patients treated with this regimen.

OUTLINE:

- Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens prior to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3 closed to accrual as of 10/1/03.)

- Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.

- Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.

- Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.

- PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may be repeated on days 1 and 2, if deemed necessary.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis regimens.

- Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV over 12 hours or orally beginning on day -4 and continuing for up to approximately 3 months.

- Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.

- Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive methotrexate.

- Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor lymphocyte infusions after day 100 may be given at the discretion of the attending physician.

Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then every 6 months for 2½ years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

OBJECTIVES:

- Determine the 18-month survival rate of patients with metastatic renal cell carcinoma treated with allogeneic stem cell transplantation.

- Determine the objective rate of response of patients treated with this regimen.

- Determine post-transplant immunological reactions and recuperation of patients treated with this regimen.

- Determine the antitumoral activity of this regimen in these patients.

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups based on availability of a compatible family member for stem cell transplantation.

- Group I: Patients with a compatible family donor receive conditioning chemotherapy comprising cyclophosphamide IV over 2 hours on days -7 and -6 and fludarabine IV once daily on days -5 to -1. Patients undergo filgrastim (G-CSF)-mobilized allogeneic stem cell transplantation on day 0. Patients also receive immunosuppression therapy with cyclosporine beginning on day -2. Patients who have persistent or progressive disease, mixed chimerism, and no evidence of grade 2 or greater graft-vs-host disease, and have been off immunosuppression therapy for 1-2 weeks receive donor lymphocyte infusion on days 7 and 21.

- Group II: Patients without a compatible family donor receive treatment (immunotherapy, vaccination therapy, or chemotherapy) at the discretion of the treating physician.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 170 patients (60 patients for group I and 110 patients for group II) will be accrued for this study within 3 years.

- The first group of participants on this study will receive up to 3 monthly doses of the study vaccine beginning about 1 month following the autologous transplant. If this is found to be safe, the next group will receive one additional study vaccine prior to the transplant and then up to 3 doses after the transplant.

- If the screening tests determine that the participant is eligible for the study, they will undergo dendritic cell collection by a procedure called leukapheresis. Leukapheresis involves the collection of white blood cells from the blood. Dendritic cells are grown from these white blood cells in the laboratory. Tumor cells will also be collected from the bone marrow through a bone marrow aspirate/biopsy.

- After cells have been collected for study vaccine generation, the participant may receive standard therapy to reduce the number of multiple myeloma cells in the body. The specific regimen will be determined by the participants multiple myeloma physician.

- The first group of patients will receive the study vaccine only after the transplant. If this is found safe then the second group will receive a single study vaccine prior to the transplant.

- Prior to the autologous stem cell transplant, we will harvest stem cells from the participants blood that will be used for the transplant later. G-CSF will be given as a daily injection beginning the day after the chemotherapy and GM-CSF injections will be started seven days after the chemotherapy. These injections will continue until after the stem cells are collected. Approximately 10 days after the chemotherapy, participants will undergo a leukapheresis procedure to collect the stem cells.

- Within a few weeks of successful stem cell collection, the participant will be admitted to the hospital for high dose chemotherapy with autologous stem cell transplantation.

OBJECTIVES:

- To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.

- To evaluate engraftment by peripheral blood chimerism analysis.

- To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.

- To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.

- To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.

OUTLINE:

- Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.

- Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.

- Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.

Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.

Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for chimerism studies by PCR analysis.

After completion of study therapy, patients are followed periodically for up to 60 months.

OBJECTIVES:

- Determine the toxicity of allogeneic hematopoietic stem cell transplantation, in terms of the incidence of grade 3-4 acute graft-versus-host disease, in young patients with relapsed or refractory solid tumors.

- Determine the incidence of transplant-related mortality at 100 days post-transplantation in these patients.

OUTLINE:

- Conditioning: Patients receive busulfan IV or orally 4 times daily on days -8 to -5 (a total of 16 doses) and melphalan IV over 15-20 minutes on days -4 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin IV on days -4 to -2.

- Allogeneic hematopoietic stem cell transplantation (SCT): Patients undergo allogeneic hematopoietic SCT on day 0.

- Post-transplant graft-versus-host disease (GVHD) prophylaxis: Patients who undergo cord blood SCT receive cyclosporine and methylprednisolone for graft-versus-host disease (GVHD) prophylaxis. Patients who undergo peripheral blood or bone marrow SCT receive cyclosporine and methotrexate (short course) for GVHD prophylaxis.

After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 4 years.

OBJECTIVES:

Primary

- Evaluate the incidence of graft acceptance in patients with hematological disorders treated with combined immunosuppression before and after HLA-haploidentical hematopoietic stem cell transplantation.

Secondary

- Evaluate efficacy of this regimen in these patients.

- Evaluate toxicity of this regimen in these patients.

- Assess survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

- Reduced-intensity conditioning: Patients receive fludarabine phosphate IV on days -6 to -1, busulfan IV on days -6 to -5, and anti-thymocyte globulin IV on days -4 to -1.

- Transplantation: Patients undergo transplantation of donor hematopoietic stem cells on day 0. Patients also receive cyclophosphamide IV on day 3 and filgrastim (G-CSF) beginning on day 4 and continuing until blood counts recover.

- Immunosuppression: Patients receive cyclosporine IV beginning on day -2 and continuing for 6 months and mycophenolate mofetil 4 times a day on days 4-84.

PRIMARY OBJECTIVES:

I. Conduct a dose escalation trial to determine the tolerability of the fructo-oligosaccharides prebiotic in allogeneic hematopoeitic stem cell transplant (HSCT) patients.

OUTLINE: This is a dose escalation study.

Patients receive fructooligosaccharides (FOS) orally (PO) twice daily (BID) for 21 days starting at 7 days before allogeneic hematopoietic stem cell transplant in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed for 100 days.

OBJECTIVES:

Primary

- To assess the safety of donor natural killer (NK) cell infusion after HLA-mismatched/haploidentical allogeneic hematopoietic stem cell transplantation from a familial donor in patients with advanced malignant disorders.

- To determine the maximum number of donor NK cells that can be safely given to these patients.

Secondary

- To assess the clinical efficacy donor NK cell infusion, in terms of tumor response, response duration, and survival, in patients with progressive or recurrent malignant disorders.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

- Phase I: Patients receive an infusion of donor natural killer (NK) cells on days 18 and 21.

- Phase II: Patients receive an infusion of donor NK cells on days 14 and 21. After completion of study treatment, patients are followed periodically.

PRIMARY OBJECTIVES:

I. To determine the toxicity associated with the administration of irradiated haploidentical cells (IHC) to patients with high-risk hematologic malignancies.

SECONDARY OBJECTIVES:

I. To determine if there is evidence of disease response associated with IHC.

TERTIARY OBJECTIVES:

I. To determine if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Within 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous hematopoietic stem cell transplantation (HSCT), patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

COHORT II: Patients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

After completion of study treatment, patients will be followed up within 8 weeks.

The optimal treatment for refractory (disease won't go away with standard treatment) or relapsed (disease comes back after going away) solid tumors is unknown. Recent studies have shown some benefit to tandem peripheral blood stem cell transplantation (PBSCT). In a tandem transplant, two transplants are done, one after the other. To do a PBSCT, stem cells ("mother cells" that can become any other type of cell) are first collected from the patient's circulating blood. The patient then undergoes high-dose chemotherapy called the preparative regimen. The preparative regimen destroys not only the tumor cells, but it also destroys all of the normal blood making cells. The collected cells are then given back to the patient to "rescue" the patient from the devastating effects of the preparative regimen. By using a stem cell rescue will are able to give much higher doses of chemotherapy than we would be able to give without the stem cell rescue. To make sure that all of the tumor cells are destroyed, patients in this study will undergo two separate transplants using two different preparative regimens. The preparative regimens will use the best agents that have been found to work against recurrent and refractory solid tumors: Busulfan, Thiotepa, Cyclophosphamide and Melphalan.

OBJECTIVES:

Primary

- Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.

- Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.

Secondary

- Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.

- Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.

- Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age>> 60 years).

- Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.

OUTLINE:

- Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.

- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.

- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.

- Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

OBJECTIVES:

Primary

- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).

Secondary

- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.

- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.

- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.

- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.

- Arm II: Patients receive no further treatment.

Patients undergo blood sample collection for chimerism studies and translational research.

After completion of study treatment, patients are followed up periodically for 1 years and then annually.

Peer Reviewed and Funded or Endorsed by Bloodwise.

OBJECTIVES:

Primary

- Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases.

Secondary

- Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen.

- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.

- Determine other toxicities of this regimen in these patients.

- Determine the overall survival and disease-free survival of patients treated with this regimen.

- Determine the impact of iron status on overall and disease-free survival.

- Determine the influence of quality of life (at time of transplantation) on overall survival.

OUTLINE:

- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3.

- Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.

- Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.

- Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 .

Quality of life is assessed at baseline.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

PRIMARY OBJECTIVES:

I. Examine the development of donor-derived HIV-1-specific immune response following hematopoietic cell transplant (HCT) for treatment of hematologic malignancy in HIV+ patients.

II. Examine the affect of HCT on the pool of latently infected cluster of differentiation (CD)4+ T cells in HIV+ patients given HCT for treatment of hematologic malignancy.

OUTLINE:

Patients undergo leukapheresis for analysis of HIV-1 latent reservoir at baseline and at days +90, +180, +365, and +730, and then annually thereafter as feasible.

OBJECTIVES:

Primary

- Determine the incidence of disease-free survival at 1 year in patients with acute or chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell transplantation from HLA-C mismatched, unrelated donors.

Secondary

- Determine the incidence of disease relapse at 1 year in patients treated with this regimen.

- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days and chronic GVHD at 1 year in these patients.

- Determine the incidence of graft failure at day 100.

- Determine the transplant-related mortality of these pat