Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation.

BACKGROUND: Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). RESULTS: Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. CONCLUSIONS: Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

T gamma (T gamma) cells suppress growth of erythroid colony-forming units in vitro in the pure red cell aplasia of B-cell chronic lymphocytic leukemia.

In vitro studies were performed in two patients with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA). During the active phase of their red cell aplasia, there was a marked reduction in the numbers of erythroid colony-forming units (CFU-E). Unfractionated sera or separated IgG fractions from these patients did not impair CFU-E proliferation from either autologous or allogeneic marrows. Increased numbers of T lymphocytes were present in marrow aspirates of these patients. Analysis of these T cells indicated that 90 and 35%, respectively, bore Fc receptors for IgG (T gamma cells). Removal of T cells by E-rosetting techniques augmented CFU-E growth in CLL-PRCA 10-fold. Similar treatment of normal marrows did not cause similar enhanced growth of CFU-E. Co-cultures of marrow T cells or T gamma cells obtained during the active phase of CLL-PRCA suppressed CFU-E growth from autologous or allogeneic marrows. After achieving drug-induced remission of the PRCA, marrow T cells were no longer inhibitory. In contrast, BFU-E (erythroid burst-forming units) or granulocyte proliferation in diffusion chambers were not suppressed by CLL-PRCA T cells. These findings suggest that the development of PRCA in B-cell CLL may result from suppression of CFU-E proliferation by T gamma cells.

Lack of effect of donor-recipient ABO mismatching on outcome following allogeneic hematopoietic stem cell transplantation.

Several recently published studies have suggested that patients who undergo ABO mismatched hematopoietic stem cell transplantation may be at increased risk for relapse, graft-versus-host disease, transplant-related mortality, and/or all-cause mortality. To investigate this issue further, we analyzed potential associations between the donor-recipient ABO mismatch pattern and the above outcome measures among 240 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation at our institution. Our analyses uncovered no significant associations between donor-recipient ABO mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute graft-versus-host disease (GVHD), or incidence of chronic GVHD. Our data do not support recent assertions that donor-recipient ABO mismatching is a major risk factor for patients undergoing allogeneic transplant, nor do they support recent assertions that ABO matching should be an important consideration in selecting allogeneic hematopoietic stem cell donors.

Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.

PURPOSE: To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS: A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS: Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.

Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.

PURPOSE: It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy. PATIENTS AND METHODS: Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF. RESULTS: The median time to a neutrophil count > or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced. CONCLUSION: Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.

Pure RBC aplasia and myasthenia gravis. Coexistence of two diseases associated with thymoma.

Pure RBC aplasia (PRCA) and myasthenia gravis (MG) are occasionally associated with thymoma, although the occurrence of all three in a single patient is rare. We describe a patient in whom PRCA and MG occurred in conjunction with the presence of serum autoantibodies, evidence for a serum inhibitor of erythropoiesis, and elevation of circulating thymosin alpha 1. Although a thymoma could not be detected before death, postmortem examination of the mediastinum found scattered cells within a nodule, suggestive of a lymphoepithelial thymic neoplasm.

The role of T lymphocytes and monocytes in the regulation of human erythropoietic peripheral blood burst forming units.

To clarify the role of T lymphocytes or monocytes in the regulation of human peripheral blood erythroid burst forming unit proliferation, equal numbers of purified T cells, B cells or monocytes were cultured in vitro with null cells in the plasma clot system. BFUE proliferation was directly proportional to the T cell concentration and inversely proportional to monocyte concentration in culture. The effect of B cells was variable and dependent on the extent of T cell contamination. Addition of a highly specific anti-human thymocyte IgG preparation (ATG) to null cells, T cells + null cells or B cells + null cells significantly reduced or eliminated BFUE proliferation. A burst promoting activity (BPA) was found in the supernatants of T cell enriched mixed lymphocyte cultures and could oppose the inhibition of BFUE proliferation by ATG. A burst inhibitory activity was found in the supernatants of monocyte enriched cultures. These studies provide further evidence that BFUE proliferation is determined by opposing actions of stimulator T cells and inhibitor monocytes and/or their soluble products.

Evidence for reduced erythroid burst (BFUE) promoting function of T lymphocytes in the pure red cell aplasia of chronic lymphocytic leukemia.

T cells stimulate the proliferation of BFUE (burst forming units-erythroid) from normal blood null cells in an in vitro culture system in the presence of erythropoietin. To determine whether abnormal BFUE proliferating effect of T cells could explain the pure red cell aplasia in chronic lymphocytic leukemia (CLL-PRCA), we investigated the erythropoietic function of T and null cells in four patients with CLL-PRCA and compared results to three patients with idiopathic pure red cell aplasia (I-PRCA) and normals. Sera from I-PRCA patients (P greater than 0.05) but not CLL-PRCA patients (P less than 0.1) inhibited erythroid stem cell proliferation in the presence of complement. BFUE in null cells of all PRCA patients were barely detectable or absent (P less than 0.0025). Normal or I-PRCA T cells increased BFUE proliferation from PRCA null cells of six patients (P less than 0.001). In contrast, CLL-PRCA T cells were poor stimulators of BFUE from autologous (P less than 0.001) or allogeneic null cells (P less than 0.02). Treatment with cyclophosphamide and prednisone induced reticulocytosis in all four CLL-PRCA patients. After treatment, in two cases, the burst promoting function of T lymphocytes was normal. Analysis of T cell subpopulations in two CLL-PRCA patients, suggested that the reduced burst promoting function was due to decreased numbers and/or function of T cells bearing Fc receptors for IgM (TM cells). These findings suggest that reduced generation of a burst promoting activity by CLL-PRCA T cells may contribute to the pathogenesis of PRCA in chronic lymphocytic leukemia.

Rapid detection of venous air embolism by mass spectrometry during bone marrow harvesting.

An episode of venous air embolism occurred in a 13-year-old girl undergoing bone marrow harvest for an autologous bone marrow transplant. The diagnosis was suspected with the sudden appearance of tachycardia and a new heart murmur during inadvertent application of positive pressure to marrow aspiration needles. Decreased carbon dioxide and increased nitrogen content of end-tidal expiratory gases was detected by continuous mass spectrometric monitoring. Cessation of faulty aspiration technique and application of positive end expiratory pressure with 100% oxygen prevented a potentially fatal complication. Venous air embolism may complicate bone marrow harvest. Mass spectrometric monitoring of end-tidal gases is useful for rapid, early detection of this complication.

Preparation of a monoclonal antibody directed against the receptor for murine colony-stimulating factor-1.

Studies were undertaken to produce monoclonal antibodies directed against the murine receptor for macrophage colony-stimulating factor (M-CSF or CSF-1). Sprague-Dawley rats were injected with lysates prepared from a murine myelomonocytic cell line (RAW cell line) that has high levels of M-CSF receptors. Spleen cells from immunized animals were fused with murine plasmacytoma cells and expanded. Supernatants from these cells caused inhibition of 125I-CSF binding to either RAW cells or normal murine marrow cells. Antibody-producing cells were cloned by limiting dilution and by colony growth in agar. The antireceptor antibodies appear specific as they neutralize colony formation by M-CSF but have little or no effect on colony growth in response to the other hemopoietic growth factors granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3) or erythropoietin. These antibodies should aid in defining the role of M-CSF in hemopoiesis in vivo.

Transfusion of bone marrow red cells during bone marrow harvests.

Large volumes of bone marrow may be required for certain types of autologous bone marrow transplants. The present study was done to determine whether red cells obtained during a bone marrow harvest would be useful in reducing homologous transfusion requirements. A group of patients receiving standard transfusion support during the harvest (group 1) was compared to a group that received processed bone marrow red cells (PBMRBC) (group 2). Using the Cobe 2991 cell processor, 90% of the harvested bone marrow red cells were extracted and transfused during the procedure. Group 2 received a median of 1500 ml of blood processed from the bone marrow or 413 ml (volume of marrow processed x hematocrit) of red cells. Infusion of the PBMRBC reduced the homologous transfusion requirement from 6.5 units to 3.0 units (p = 0.02). In addition, group 1 had a 20% decrease in hematocrit following transfusion compared to the pre-harvest hematocrit, as opposed to an 8% decrease in group 2 (p = 0.02). This study indicates that PBMRBC can reduce the homologous transfusion requirements during an autologous bone marrow harvest.

Demonstration of two distinct antibodies in autoimmune hemolytic anemia with reticulocytopenia and red cell aplasia.

To determine the mechanism of the aplastic crisis in a patient with autoimmune hemolytic anemia (AIHA) and reticulocytopenia who developed red cell aplasia simultaneously, serum- and IgG-separated fractions were examined for the presence of erythroid progenitor cell inhibitors. The patient's red cell autoantibody was a complement-independent IgG that reacted with the little-e antigen of the Rh complex. A complement-dependent serum IgG inhibitor directed against erythroid colony- and burst-forming units but not granulocyte-macrophage units was detected in samples before treatment with extracorporeal staphylococcal protein-A immunoadsorption and corticosteroids. The erythroid progenitor cell inhibitor persisted in samples multiply adsorbed against type-ee red cells and was not detected in heat eluates prepared from these red cells. A reticulocytosis occurred when serum IgG levels were reduced to 27% of pretreatment values. At this point, the erythroid progenitor cell inhibitor was not detectable in vitro. These findings suggest that the development of the aplastic crisis in some patients with AIHA may be associated with the presence of two distinct IgG antibodies, one directed at the mature red cell and the other at the erythroid progenitor cells.

Hematologic and cytogenetic remission of 5q-refractory anemia after syngeneic bone marrow transplantation.

Refractory macrocytic anemia with hypolobulated megakaryocytic nuclei and partial deletion of the long arm of chromosome 5 has been termed the 5q- syndrome. Although long survival has been reported in a few cases of 5q- refractory anemia, accumulating evidence suggests that this syndrome is a preleukemic state with risk of transformation to acute nonlymphocytic leukemia as well as complications of bone marrow failure. This report describes the first apparently successful therapy for this disorder in a young man who originally presented with a clinical picture consistent with pure red cell aplasia and normal marrow chromosomes but with hypolobulated megakaryocytic nuclei. He was treated with vitamins, androgens, and sequential trials of immunosuppressive therapy, all without response. Two years after diagnosis, repeated marrow cytogenetic studies showed a 5q- abnormality in 70 percent and later in 100 percent of marrow metaphases. Because of transfusion-induced hemosiderosis and the availability of a cytogenetically normal monozygotic twin, bone marrow transplantation was undertaken. In light of the clonal (and suspected preleukemic) nature of the 5q- syndrome, the patient's marrow was ablated with a busulfan plus cyclophosphamide regimen used for patients with nonlymphocytic leukemia. Sustained engraftment of cytogenetically normal marrow ensued. Two years after transplantation, and following six months of regular phlebotomy, the patient was hematologically normal with a normal serum ferritin level.

Phase II pilot study of high-dose busulfan and CY followed by autologous BM or peripheral blood stem cell transplantation in patients with advanced chemosensitive breast cancer.

The combination of busulfan and CY ('BU-CY') has been widely employed as a conditioning regimen for patients undergoing BMT for hematologic malignancies. However, little information is available regarding the utility of BU-CY in treating patients with advanced breast cancer. Fifteen patients with heavily pretreated Stage IIIB or Stage IV chemosensitive breast cancer were treated with busulfan (16 mg/kg) and CY (6000 mg/m2) followed by rescue with autologous BM or autologous peripheral blood stem cells. Toxicity and engraftment parameters were similar to those observed in patients receiving BU-CY for other indications. The overall response rate was 87%, with 53% of patients achieving CR. The median progression-free survival was 164 days, and the median overall survival was 292 days. We conclude that BU-CY is able to induce remissions in a high percentage of patients with heavily pretreated advanced breast cancer. However, remissions are brief, and alternative strategies for patient selection and/or management will be necessary to improve on these results.

Phase II study of high-dose cyclophosphamide, etoposide, and carboplatin (CEC) followed by autologous hematopoietic stem cell rescue in women with metastatic or high-risk non-metastatic breast cancer: multivariate analysis of factors affecting survival and engraftment.

Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or IV (n = 37) breast cancer received cyclophosphamide 6000 mg/m2, etoposide 2400 mg/m2, and carboplatin 1200 mg/m2 followed by infusion of autologous hematopoietic stem cells (AHSC). Women with high-risk stage II disease had eight or more involved axillary lymph nodes (n = 9) or axillary and breast relapse following lumpectomy, chemotherapy, and radiation therapy (n = 1). Women with measurable stage III or stage IV disease were required to demonstrate complete or partial response to conventional-dose chemotherapy prior to transplant. The overall (complete plus partial) response rate for the 31 patients not in complete remission at the time of transplant was 55%. With a median follow-up of 545 days, the 2-year actuarial progression-free survival rates for patients with stage II, IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently predictive of longer progression-free survival by multivariate analysis included lower stage disease, status of disease at transplant (in CR vs not in CR), and positive estrogen receptor status. Factors predictive of more rapid neutrophil engraftment by multivariate analysis included post-transplant administration of hematopoietic growth factors, greater number of infused CFU-GM, mobilization with G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization), and lower stage disease. Only one patient (1.4%) died prior to day 100 from any cause. High-dose cyclophosphamide, etoposide, and carboplatin followed by infusion of AHSC constitutes an active and well-tolerated regimen in the treatment of women with high-risk non-metastatic or metastatic breast cancer.

Graft failure following neutrophil-specific alloantigen mismatched allogeneic BMT.

We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophil alloantigen mismatch played a role in the development of the graft failure.

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients.

This study was conducted to determine if the accelerated telomere attrition that occurs as a consequence of allogeneic stem cell transplantation leads to measurable functional defects. Telomere lengths in mononuclear leukocytes obtained from 15 long-term allogeneic stem cell transplant recipients and their respective donors were determined by Southern hybridization and densitometric analysis. Functional assays evaluated the ability of these cells to proliferate in response to a mitogenic stimulus and to differentiate under appropriate cytokine stimulation. Lymphocyte proliferation in response to phytohemagglutinin was determined by measurement of (3)[H]thymidine uptake. The ability of circulating myeloid cells to differentiate was determined after incubation of peripheral blood mononuclear cells with IL-3 and GM-CSF. A total of 13 patients demonstrated telomeric loss, ranging from 0.1 to 3.7 kbp. Strikingly, lymphocytes from 14 of the 15 patients demonstrated a significant decrease in proliferation when compared to their respective donors (68%+/-22, P=0.001). All patients demonstrated at least a 50% decrease in the number of myeloid colony-forming units when compared to their respective donors (P<0.0001). A decreased ability of hematopoietic cells to proliferate and differentiate is phenotypically consistent with an aged immune system. This may correlate with diminished clinically relevant immune responses to infection or vaccination, as seen in the elderly.

Association between antibodies reactive with neutrophils, rate of neutrophil engraftment, and incidence of post-engraftment neutropenia following BMT.

Previous reports have suggested that antibodies reactive with neutrophils (ARN) are frequently detectable in patients undergoing bone marrow or blood stem cell transplantation (BMT), and that such antibodies result in steroid-responsive delayed neutrophil engraftment or steroid-responsive post-engraftment neutropenia in some patients. However, the true incidence and significance of ARN in the BMT setting remain poorly established because most of the published data are in the form of retrospective case reports. Therefore, we prospectively studied the incidence of ARN, the rate of neutrophil engraftment, and the incidence of post-engraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36 evaluable patients (44%) had detectable ARN following transplant vs none of 25 concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN in the post-transplant period recovered to an absolute neutrophil count (ANC) of 500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN; multivariate analysis controlling for the potential effects of diagnosis, conditioning regimen, amount of prior therapy, and other factors revealed that only the administration of hematopoietic growth factors (P = 0.008) and the presence of ARN in the post-transplant period (P = 0.016) were independently predictive of the rate of neutrophil engraftment following BMT. Four of the 16 patients with detectable ARN (25%) satisfied previously published criteria for post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for at least 2 consecutive days, following initial engraftment to an ANC of at least 1000 x 10(9)/l for at least 2 consecutive days. In contrast, none of the 20 patients without detectable post-transplant ARN developed post-engraftment neutropenia. Multivariate analysis revealed that only the presence of ARN in the post-transplant period (P = 0.022) was independently predictive of post-engraftment neutropenia. All four patients with ARN-associated post-engraftment neutropenia responded to steroid-based therapy. These prospectively gathered data support previously published primarily case report data suggesting that ARN occur frequently following BMT and are associated with an increased incidence of delayed neutrophil engraftment and post-engraftment neutropenia. As is the case in the non-transplant setting, ARN-associated neutropenia occurring following BMT may respond to steroid-based therapy.

Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile.

An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD) during an autologous bone marrow transplant for primary refractory nodular sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction, coagulation studies revealed depression of vitamin K dependent procoagulant factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over h on 4 consecutive days and continuous heparin infusion (1000 unit bolus followed by 150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During treatment, procoagulant factors II, VII, IX and X levels increased indicating the return of hepatic synthesizing capacity. Factor V levels, which were elevated pre-therapy, also rose dramatically. Plasma antigen levels of protein C, a natural anticoagulant, remained severely depressed. No clinical evidence of bleeding and only minimal systemic fibrinolysis was noted. Despite concerns regarding the use of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of coagulation parameters during severe VOD suggested that low dose rt-PA improved portions of the systemic hemostatic profile.

Phase I/II study of high-dose cyclophosphamide, etoposide and cisplatin followed by autologous bone marrow or peripheral blood stem cell transplantation in patients with poor prognosis Hodgkin's disease or non-Hodgkin's lymphoma.

We conducted a phase I/II study to determine the efficacy, toxicity and maximum tolerable doses of CY, etoposide and cisplatin (CEP) in the management of patients with relapsed or refractory malignant lymphoma. Thirty patients with relapsed or refractory Hodgkin's disease (n = 10) or non-Hodgkin's lymphoma (n = 20) received CY 6000 mg/m2, etoposide 900-2700 mg/m2 and cisplatin 150 mg/m2 followed by autologous BM or autologous peripheral blood stem cell rescue. The dose of etoposide was escalated after each 3 to 4 patients. The maximum tolerated dose of etoposide, when administered with the indicated doses of CY and cisplatin, was 2400 mg/m2. Three of the 30 patients (10%) died of treatment-related toxicity. Although 14 of the 30 patients had residual bulky and/or chemotherapy-resistant disease at the time of the transplant, 26 patients (87%) responded to this regimen, including 18 patients (60%) who achieved CR and 8 patients (27%) who achieved partial remission. Seven patients (23%) remain alive and free of progression at a median of 21 months post-transplant. Three additional patients relapsed after transplant but are enjoying prolonged disease-free survival at a median of 31 months post-transplant following additional post-transplant therapy. We conclude that high-dose CY, etoposide and cisplatin followed by autologous BM or peripheral blood stem cell rescue is an active and acceptably tolerated regimen in the treatment of relapsed or refractory malignant lymphoma.