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Purpose: Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care., Methods: SIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab-led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population., Results: The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively., Conclusion: The 131 I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.

Purpose: To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma., Patients and Methods: Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes., Results: AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival., Conclusion: These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology.

Purpose: Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas., Patients and Methods: We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas)., Results: Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis., Conclusions: Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.

PURPOSE Adult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. METHODS We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, > or = 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). CONCLUSION This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.

Purpose: This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)., Patients and Methods: Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors., Results: After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics., Conclusion: Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.

Purpose: To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma (NHL)., Patients and Methods: The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants., Results: No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts., Conclusion: These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.

Purpose: Primary mediastinal B-cell lymphoma (PMBL) is recognized as a separate disease entity in the REAL classification. There is uncertainty about the relevance and especially the optimal management of this disorder. In this review, we discuss clinical presentation, pathology, pathobiology, and management of PMBL in order to provide a platform for initiation of further clinical and biologic studies., Materials and Methods: Studies were identified through a MEDLINE search and from the bibliographies of relevant articles., Results: PMBL is a tumor of young adults who present with a rapidly proliferating tumor. At diagnosis, the tumor is usually limited to intrathoracic organs. Spread to parenchymal organs such as liver, kidneys, and CNS is common at recurrence. Fibrosis and the presence of so-called clear cells are distinctive morphologic features of PMBL, although they are not pathognomonic or even necessary for diagnosis. On the other hand, biologic features relating to oncogene rearrangement and overexpression as well as cytogenetic features clearly differentiate PMBL from other types of diffuse large B-cell lymphoma. Phase II studies and retrospective series indicate cure rates that range from 38% to 88%. The role of chemotherapy, radiation, and high-dose chemotherapy with stem cell rescue in the management of PMBL is reviewed., Conclusion: PMBL has unique clinical and biologic characteristics that are radically different from those of other types of diffuse large B-cell lymphoma. Although relatively rare, its aggressive growth and its occurrence in young patients increase the clinical relevance of this entity. The consistent recognition and study of PMBL will allow the development of new approaches to its management.

Purpose: To evaluate whether administration of interleukin-2 (IL-2) with granulocyte colony-stimulating factor (G-CSF) improves mobilization of immune effector cells into the stem-cell graft of patients undergoing high-dose chemotherapy and autografting., Patients and Methods: We performed a trial of stem-cell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin and stem cells followed by IL-2. The trial defined immune, hematologic, and clinical effects of IL-2 in this setting., Results: Of 32 patients enrolled, nine received G-CSF alone for mobilization. Twenty-one of 23 patients mobilized with IL-2 plus G-CSF had stem cells collected with more mononuclear cells than those receiving G-CSF (19.3 v 10.4 x 10(8)/kg; P =.006), but fewer CD34(+) progenitor cells (6.9 v 22.0 x 10(6)/kg; P =.049). The IL-2 plus G-CSF-mobilized patients had greater numbers of activated T (CD3(+)/CD25(+)) cells (P =.009), natural killer (NK; CD56(+)) cells (P =.007), and activated NK (CD56 bright(+)) cells (P: =.039) than those patients mobilized with G-CSF. NK (P =.042) and lymphokine-activated killer (LAK) (P =.016) activity was increased in those mobilized with IL-2 + G-CSF, whereas G-CSF-mobilized patients had a decline in cytolytic activity. In the third week posttransplantation, immune reconstitution was superior in those mobilized with IL-2 plus G-CSF based on greater numbers of activated T cells (P =.003), activated NK cells (P =.04), and greater LAK activity (P =.003). The 16 of 21 IL-2 + G-CSF-mobilized patients with adequate numbers of stem cells (> 1.5 x 10(6) CD34(+) cells/kg) collected engrafted rapidly posttransplantation., Conclusion: The results demonstrate that G-CSF + IL-2 can enhance the number and function of antitumor effector cells in a mobilized autograft without impairing the hematologic engraftment, provided that CD34 cell counts are more than 1.5 x 10(6) cells/kg. Mobilization of CD34(+) stem cells does seem to be adversely affected. In those mobilized with IL-2 and G-CSF, post-stem-cell immune reconstitution of antitumor immune effector cells was enhanced.

Purpose: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy., Patients and Methods: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America., Results: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival., Conclusion: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.

Purpose: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival., Patients and Methods: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed., Results: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome., Conclusion: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.

Purpose: To evaluate the feasibility of allogeneic peripheral-blood progenitor-cell (PBPC) transplantation and to assess graft-versus-tumor effects in patients with metastatic breast cancer., Patients and Methods: Ten patients with metastatic breast cancer that involved the liver or bone marrow were treated with high-dose chemotherapy and allogeneic PBPC transplantation. The median age was 42 years (range, 29 to 55). The median number of metastatic sites was three (range, one to five). The conditioning regimen was cyclophosphamide (6,000 mg/m2), carmustine (BCNU; 450 mg/m2), and thiotepa (720 mg/m2) (CBT regimen). Patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine- or tacrolimus-based regimens., Results: All patients had engraftment and hematologic recovery. Three patients developed grade > or = 2 acute GVHD and four patients had chronic GVHD. After transplantation, one patient was in complete remission (CR), five achieved a partial remission (PR), and four had stable disease (SD). In two patients, metastatic liver lesions regressed in association with skin GVHD after withdrawal of immunosuppressive therapies. The median follow-up time was 408 days (range, 53 to 605). The median progression-free survival duration was 238 days (range, 53 to 510)., Conclusion: We conclude that allogeneic PBPC transplantation is a feasible procedure for patients with poor-risk metastatic breast cancer. The regression of tumor associated with GVHD provides suggestive clinical evidence that graft-versus-tumor effects may occur against breast cancer. Compared with autologous transplantation, allogeneic PBPC transplantation is associated with the additional risks of GVHD and related infections. Allogeneic transplantation should only be performed in the context of clinical trials and its ultimate role requires demonstration of improved progression-free survival.

Purpose: This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy., Patients and Methods: A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995., Results: Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression., Conclusion: Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.

Purpose: To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation., Patients and Methods: Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group)., Results: All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant., Conclusion: Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

Purpose: To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies., Patients and Methods: In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group., Results: Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01)., Conclusion: Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.

Purpose: To evaluate the role of allogeneic bone marrow transplantation (BMT) in recurrent low-grade lymphoma., Patients and Methods: Between 1989 and 1994, 10 patients with chemotherapy-refractory and recurrent low-grade lymphoma were treated with myeloablative therapy and allogeneic BMT. All patients had poor prognostic features and had been extensively pretreated., Results: Eight patients achieved a complete remission and none have relapsed at a median follow-up time of 816 days (range, 346 to 1,865). Two patients died of early complications. The actuarial survival and failure-free survival rates are both 80% +/- 12.6%. For surviving patients, the duration of the current remission exceeds that of any previous remission achieved., Conclusion: These results compare favorably with those for autologous BMT. Allogeneic BMT offers considerable promise for the treatment of patients with poor-prognosis low-grade lymphoma. Its role should be further defined in prospective studies.

Purpose: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies., Patients and Methods: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0., Results: Patients with early leukemia had a disease-free survival rate of 53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% +/- 5% and overall survival rate of 17% +/- 5%. The actuarial relapse rate for the early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early-leukemia group was 10% versus 50% for patients with more advanced disease., Conclusion: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

Purpose: This study was undertaken to evaluate the feasibility and therapeutic effect of high-dose chemoradiotherapy with autologous or allogeneic bone marrow transplantation (BMT) in patients with advanced chronic lymphocytic leukemia (CLL) who relapse after fludarabine treatment., Patients and Methods: Twenty-two patients with advanced CLL received high-dose cyclophosphamide, total-body irradiation, and BMT. Eleven patients with relapsed CLL received autologous BMT with marrow collected during a prior fludarabine-induced remission; leukemia cells were depleted from the autologous marrow in seven patients using an anti-CD19 monoclonal antibody and immunomagnetic separation. Eleven patients received allogeneic or syngeneic BMT, seven of whom had refractory Rai stage III or IV disease., Results: Six autologous transplant recipients achieved a complete remission (CR), four a nodular CR (nCR), and one a partial remission (PR). Two recurred with CLL, and three developed Richter's transformation. Two patients had recurrence of immune cytopenias while in morphologic remission; one of these patients died of cytomegalovirus pneumonia. Six of 11 patients survive in remission 2 to 29 months following BMT. Of the 11 patients who received allogeneic or syngeneic BMT, seven achieved a CR, two a nCR, and one a PR; 10 survive 2 to 36 months following BMT., Conclusion: These data indicate that high-dose chemotherapy with allogeneic BMT is effective at producing CRs in patients with CLL. Autologous transplantation in CLL is feasible and is capable of producing remissions in patients with advanced CLL. Further studies are warranted to assess the role of BMT in the treatment of CLL.

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.