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Biomedical subjects

H G Klingemann

Publications and source records attributed to H G Klingemann.

At least 19 recordsLinked to original sources
PubMed1995

High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.

Actuarial Analysis↗
PubMed1995

Introducing graft-versus-leukemia into autologous stem cell transplantation.

Although autologous transplantation of stem cells is widely used to support high-dose chemotherapy and radiation for the treatment of hematologic malignancies, relapse is a severe impediment to its wide use, especially in patients receiving transplants for leukemia. This is related to the infusion of leukemic cells in the autograft and the lack of an allogenic graft-versus-leukemia (GVL) effect. This review discusses the current approaches that are under study to introduce a GVL effect into autologous transplantation.

Combined Modality Therapy↗
PubMed1995

Is there a place for immunotherapy with interleukin-2 to prevent relapse after autologous stem cell transplantation for acute leukemia?

Chemotherapy-resistant cells cause disease recurrence in a significant proportion of patients with acute leukemia treated with autologous stem cell transplantation due to the lack of immune-mediated effects which contribute significantly to the prevention of post-treatment disease recurrence. This conclusion is based on the observation that relapse after high dose chemotherapy supported by a stem cell transplant from a twin donor is 3-4 times higher than after transplant from an allogeneic donor. This anti-leukemic mechanism of transplanted donor cells has been termed graft-versus-leukemia (GVL) effect, and efforts are being directed toward utilizing such an immune-mechanism after autologous transplantation. Since interleukin-2 (IL-2) can induce remissions in selected patients with advanced leukemia, it has become a candidate cytokine to be used in attempts to introduce GVL after autologous stem cell transplantation. Here we review the available clinical data with IL-2 and critically evaluate whether IL-2 has a place as adjunct treatment to prevent relapse after autologous transplantation for acute leukemia.

Actuarial Analysis↗
PubMed1995

Treatment of acute promyelocytic leukemia in patients presenting at Vancouver General Hospital from 1983 to 1992.

Between 6/83 and 8/92, 23 of 361 patients (6.4%) presenting at Vancouver General Hospital with acute myelogenous leukemia had acute promyelocytic leukemia (APL). Treatment plan was: 1) induction with high-dose cytosine arabinoside and an intercalator; and 2) consolidation with allogeneic bone marrow transplantation (BMT) for those aged < or = 50 years with a sibling donor or repeat of induction for the the others. Complete remission (CR) was achieved in 20 patients (87%). Eleven patients in CR were eligible for allogeneic BMT; 4 were considered unsuitable, 2 refused, and 5 underwent this treatment--1 died of acute graft-versus-host disease, 1 relapsed and 3 are leukemia-free and well 1.6, 3.3 and 3.9 years after diagnosis. Fifteen patients did not undergo allogeneic BMT in CR; 4 received no further treatment and all died, 2 relapsed before consolidation therapy and both died, 1 underwent autologous BMT and died of complications, and 8 received consolidation treatment as planned--1 died of sepsis, 2 relapsed and 5 are leukemia-free and well 1.0, 3.8, 4.5, 4.9 and 8.5 years after diagnosis. The actuarial overall survival for all 23 patients was 38% (95% confidence interval [CI] 18-57%). The actuarial 2-year leukemia-free survival was 60% (95% CI 20-85%) for the 8 patients who underwent consolidation chemotherapy as planned and 53% (95% CI 68-86%) for the 5 patients who underwent allogeneic BMT in CR. These results suggest that patients with APL who are able to undergo consolidation chemotherapy have a relatively good prognosis and allogeneic BMT may reasonably be held in reserve for salvage therapy.

Adult↗
PubMed1995

Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation.

Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

1994 Consensus Conference on Acute GVHD Grading.

Grading acute graft-versus-host disease (GVHD) is usually based on quantification of rash, serum bilirubin and diarrhea. Standard criteria have been developed and used for > 20 years by most transplant centers. However, neither the standard GVHD grading system nor any of several revisions has been validated in the context of GVHD prophylaxis with cyclosporine. The 1994 Consensus Conference on Acute GVHD Grading held in Keystone in January 1994 provided an opportunity to: (1) review data regarding these standard criteria; (2) determine if there are sufficient data to revise these criteria; and (3) develop recommendations for reporting results of GVHD prevention trials. Data were provided for 8249 patients from 12 large transplant centers and 2 transplant registries. Standard GVHD grading criteria were found to distinguish different mortality risks and treatment response rates. Analysis of new data suggested that persistent nausea with histologic evidence of GVHD but no diarrhea be included as stage 1 gastrointestinal GVHD. Additional studies were recommended to evaluate heterogeneity of outcome within GVHD grades prior to making further revisions. To improve comparability between publications, reports of GVHD prevention trials should include an accurate description of the grading system used and should report actuarial rates of grades II-IV and III-IV GVHD corrected for graft failure and potential interventions for early relapse. Additional information should include indications for therapy of GVHD and response.

Acute Disease↗
PubMed1995

Treatment of myeloma using intensive therapy and allogeneic bone marrow transplantation.

Over a 5-year period we evaluated 65 myeloma patients aged < or = 55 years as potential candidates for intensive therapy and allogeneic BMT. Twenty six (40%) patients were transplanted; the median duration of disease was 4 months (range 2-58 months) and median number of prior regimens was 1 (range 1-5); all but five patients had chemosensitive disease. Conditioning regimens included combinations of BU+CY+MEL in 14 patients, BUCY2 in eight and CY+TBI in four. Donors were HLA-matched siblings in 19 cases, one antigen mismatched siblings in three and unrelated donors in four. All patients received CsA, plus either methylprednisolone (n = 5) or MTX with or without other agents (n = 19). Grade III or IV regimen-related toxicity (RRT) was relatively infrequent (3 patients) and was not seen in nine patients conditioned with BU (total dose 12 mg/kg) + MEL (100 mg/m2) + CY (90 mg/m2). Grade II-IV acute GVHD occurred in 20 patients, and was the cause of death in three. Chronic GVHD also caused three deaths. Thirteen of 21 evaluable patients (62%) achieved a CR and six achieved a PR. Actuarial progression-free survival (PFS) was 40% (95% confidence interval (CI) 19-61%) at a median follow-up of 14 months (range 3-56 months); the PFS was 52% (95% CI 24-74%) in chemoresponsive patients, compared with 0% in chemoresistant patients (P = 0.0066).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience.

We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.

Adolescent↗
PubMed1994

Transfer of the tumor necrosis factor alpha gene into hematopoietic progenitor cells as a model for site-specific cytokine delivery after marrow transplantation.

Relapse of leukemia is the major cause of failure after autologous stem cell transplantation due to reinfusion of residual clonogenic cells and the absence of an immune-mediated graft-versus-leukemia effect. To provide an antileukemia effect, immune-activating cytokines have been given to patients after transplantation. Systemic administration of such cytokines early after transplantation is often accompanied by substantial side effects, and it is unknown whether sufficient concentrations reach the sites of residual disease in the marrow. As a method of site-directed immunotherapy provided early after stem cell transplantation, we have tested in a murine model whether (1) marrow can be retrovirally transduced with the tumor necrosis factor alpha (TNF alpha) gene, (2) local production of TNF alpha by marrow cells after transplantation can be achieved, and (3) adverse effects of TNF alpha occurred. Balb/c mice were treated with 5-fluorouracil and bone marrow (BM) was obtained 4 days later. Whole BM was transduced in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor by coculture with the packaging cell line GP+E-86, producing the cDNA for TNF alpha. Irradiated (1,300 cGy) syngeneic recipient mice were given 10(6) transduced BM cells on day 0. Integration of the TNF alpha gene into the host genome was documented by Southern blotting in spleen and BM cells on days 7 and 12 and in BM on day 40 after marrow infusion, but was no longer found on day 90. Messenger RNA for TNF alpha was present on day 12, but could no longer be shown on day 40 or 90. Although no measurable (L929 bioassay) levels of TNF alpha were found in serum of mice who had received TNF alpha transduced marrow, the supernatant of 10(6) unstimulated BM cells obtained 12 days after marrow infusion was found to have 7 pg of TNF alpha compared with 1.8 pg in nontransduced marrow. Mice that had received TNF alpha transduced marrow showed no side effects suggestive of systemic TNF alpha release, and cellularity of the TNF alpha-transduced marrow was not different from control mice that had received unmanipulated marrow or cells transduced with the neomycin resistance gene only. The studies suggest that gene transfer of immune-activating cytokines into hematopoietic cells could be used as a means to achieve their temporary local production early after transplantation by cells located in the BM.

Animals↗
PubMed1994

Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study.

Incubation of chronic myeloid leukemia (CML) marrow for 10 days in vitro causes a marked and selective loss of very primitive Philadelphia chromosome (Ph)+ as compared with Ph- progenitors. We have autografted 22 patients with CML (16 in first chronic phase [group 1] and 6 with more advanced disease [group 2]) with marrow treated in this way to facilitate restoration of Ph- hematopoiesis after intensive therapy. Hematologic recovery to greater than 0.5 x 10(9)/L neutrophils occurred in 16 patients, and to greater than 20 x 10(9)/L platelets in 15 of 21 evaluable patients at a median of 29 and 48 days postautograft, respectively. Regenerating marrow cells were 100% Ph- in 13 patients and 75% to 94% Ph- in 3. Between 4 and 36 months (median 12) postautograft, Ph+ cells became detectable in all but 1 (who died in remission) of the 13 patients who achieved complete cytogenetic remission. Four of 7 evaluable patients treated with low-dose interferon alpha were returned to complete cytogenetic remission. Thirteen group 1 patients (81%) are alive 1.0 to 5.7 years (median 2.6) after autografting: 4 in complete cytogenetic remission, 2 in hematologic remission, 6 in chronic phase, and 1 in myeloid blast phase. Three group 2 patients (50%) are alive at 2.6, 3.8, and 4.3 years after autografting: 1 in partial cytogenetic remission, 1 in chronic phase, and 1 in accelerated phase. Thus, autografts of cultured marrow can result in prolonged restoration of Ph- hematopoiesis for some patients with CML.

Adult↗
PubMed1994

Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy.

The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.

Adolescent↗
PubMed1994

Establishment and characterization of a human leukemic cell line (SR-91) with features suggestive of early hematopoietic progenitor cell origin.

The characterization of a cell line (designated SR-91) from a patient with clinical and morphological diagnosis of acute lymphoblastic leukemia (CD3-, CD2+, CD7+, germline TCR genes) who relapsed early after allogeneic bone marrow transplantation, is reported. The line was established from blood cells obtained at diagnosis and placed in suspension culture with medium conditioned by 5637 cells. SR-91 cells are negative for lymphoid surface markers (CD3-, CD2-, CD7-) but positive for markers indicative of myeloid progenitor cells, such as CD33 and CD34. It is likely that the conditioned medium has induced myeloid differentiation from a lymphohematopoietic progenitor cell. After establishment, cells proliferated in response to GM-CSF stimulation but they are not factor-dependent and do not produce GM-CSF. No proliferative response to IL-1, IL-2, IL-3, IL-4, IL-6 or M-CSF was observed. Cells were completely resistant to anti-proliferative effects of tumor necrosis factor-alpha and interferon-alpha or -gamma, and showed no lysis after incubation with freshly isolated natural killer cells or IL-2-activated natural killer cells.

Adult↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor after autologous marrow transplantation for Hodgkin's disease.

Recombinant yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients after autologous bone marrow transplantation for Hodgkin's disease given as a 24-h continuous intravenous infusion from the day of marrow infusion until the patient had obtained an absolute neutrophil count of 1.5 x 10(9)/L for 2 consecutive days or until day 30, whichever occurred first. Results were compared with results from 18 historical control patients who did not receive GM-CSF but were otherwise treated in a similar fashion. The infusion of GM-CSF led to a significantly faster neutrophil and monocyte recovery compared to the patients in the historical control group. The median days to achieve an absolute neutrophil count for the GM-CSF group and the control group were 0.5 x 10(9)/L; 9.5 and 14 days; 1.0 x 10(9)/L: 10 and 18 days; 1.5 x 10(9)/L: 11 and 29 days. No significant difference was found with respect to platelet engraftment and red cell transfusion requirements. GM-CSF therapy was discontinued at a median of 12 days. Hospitalization was also shorter for the GM-CSF group (22.5 vs. 26.5 days) and no patient in the GM-CSF group had to be readmitted after initial discharge. The incidence of documented infections was similar among both patient groups and no difference was noted in terms of antimicrobial usage. Some side effects occurred with the continuous infusion of GM-CSF, particularly fluid retention, dyspnea, fever, diarrhea, and bone pain leading to early discontinuation of GM-CSF in 2 patients. The data suggest that a continuous 24-h infusion of GM-CSF significantly accelerates myeloid engraftment, leading to earlier discharge from the hospital.

Adolescent↗
PubMed1994

Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration.

Relapse rates in patients after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) continue to be high despite the use of aggressive conditioning regimens. Based on studies in the murine system a clinical protocol was developed that utilizes immunotherapy to obtain a graft-versus-leukemia (GVL) effect both pre-BMT (to purge leukemic cells from the autograft) and post-BMT (to eradicate residual leukemia in the patient). As part of a phase I study, 10 consecutive patients (median age 41 years, range 15-60 years) with 'high risk' AML (i.e. any of the following: FAB M5, WBC of > or = 50 x 10(9)/l at diagnosis or 'unfavorable' cytogenetic abnormalities) were transplanted at a median of 32 days (range 13-128 days) after achieving first remission. Marrow cells to be autografted were first cultured for 8 days at 37 degrees C in standard long-term culture medium (containing 12.5% horse serum, 12.5% fetal calf serum and 10(-6) M hydrocortisone) to which 1000 U/ml of interleukin-2 (IL-2) was also added. During this time patients received busulfan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg for 2 days). On the day of transplantation (day 0), the cultured marrow cells were collected from the flasks and infused over 1 h. Between days 0 and 7 patients were given escalating doses of subcutaneous IL-2 (2, 4 and 6 x 10(5) U/m2/day, 3-4 patients/dose level). Side-effects attributable to IL-2 were generally mild, dose-dependent and consisted of fever and malaise.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells.

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.

Antigens, CD↗
PubMed1993

Autografting in chronic myeloid leukemia with cultured marrow: update of the Vancouver Study.

When chronic myeloid leukemia (CML) marrow is set up in long-term culture (LTC), Philadelphia chromosome (Ph)-positive (Ph+) cells typically decline and Ph-negative (Ph-) hematopoietic cells often become detectable. In 1987, we initiated a study to evaluate the feasibility of using 10-day cultured marrow autografts to allow intensive treatment of CML. Patients were selected on the basis of a previous assessment of the frequencies of normal and leukemic LTC-initiating cells (LTC-IC) remaining in their marrow after 10 days of LTC. Of the 87 patients evaluated, 36 (41%) were considered eligible, and 22 (15 in first chronic phase [CP], Group 1; and 7 with more advanced disease, Group 2) were autografted with 10-day cultured marrow after intensive therapy. Satisfactory hematological recovery occurred in 16 patients, and of these, only Ph- cells were detected in 13 (nine in Group 1), with 76-94% Ph- cells in the other three (two in Group 1). Ph+ cells reappeared between 4 and 36 months post-autograft in all but one of the 13 patients in whom complete (morphological and cytogenetic) remission had been achieved; the remaining patient died in remission. Nine of these twelve patients were then treated with alpha-interferon (IFN-alpha) 1-3 x 10(6) units/m2, 3-7 days/week; four returned to complete remission, three developed increasing numbers of Ph+ cells, and two are still too early to evaluate. Fifteen patients (12 in Group 1) remain alive and well, nine in hematological remission (eight in Group 1), 9 to 64 months (median 28) post-autograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Trying to overcome residual disease after bone marrow transplantation for hematologic malignancies.

Relapse after marrow transplantation occurs despite total body irradiation and high doses of chemotherapy used to prepare the recipient. Recurrence rate is particularly high after autologous transplantation. In order to eliminate minimal residual disease persistent after marrow grafting, immunotherapy is currently being explored as a treatment modality that is non-cross-reactive with radiation and chemotherapy. This review describes first clinical results on the use of interferons and interleukin-2 in marrow transplant recipients as well as attempts to induce graft-versus-leukemia effects.

Bone Marrow Transplantation↗