Autologous Hematopoietic Stem Cell Support Research Articles

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

Phase II Study on the Effect of Disease Sites, Age, and Prior Therapy on Response to Iodine-131-Metaiodobenzylguanidine Therapy in Refractory Neuroblastoma

To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (131I-MIBG) treatment of patients with resistant neuroblastoma. One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of 131I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease. Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year. The high response rate and low nonhematologic toxicity with 131I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma.

Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.

Molecularly Guided Therapy of Neuroblastoma: A Review of Different Approaches

Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric tumors and affects more than ten thousand children a year. It originates from the sympathetic nervous system and is characterized by heterogeneous pathological and clinical presentation. Stage 4 NB represents approximately 50% of the cases and shows metastatic dissemination at onset; its prognosis is grim, with 20% of the patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy with autologous hematopoietic stem cell support. Novel therapeutic strategies are urgently needed to improve the prognosis of stage 4 NB patients. Here we review the most promising approaches to NB treatment that have already reached clinical testing or have proved to be successful in preclinical models of the disease. All of these approaches are molecularly guided, since their rational development has benefited from the enormous amount of information on the biology of neuroblastoma gathered through molecular biology and genetics studies. The following topics are reviewed: MYCN oncogene amplification as parameter for therapeutic decision, minimal residual disease, immunotherapy, gene therapy, differentiation and apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for generating novel therapeutic approaches. Although several efforts are still needed to reach a significant cure of patients with neuroblastoma, molecularly guided approaches have opened new ways to neuroblastoma treatment and can represent useful models for other cancers of either childhood or adulthood.

Randomized trial of high‐dose chemotherapy and autologous hematopoietic stem cell support for high‐risk primary breast carcinoma

The authors previously reported results from a randomized trial of standard-dose chemotherapy with combined 5-fluorouracil (1000 mg/m2 per cycle), doxorubicin (50 mg/m2 per cycle), and cyclophosphamide (500 mg/m2 per cycle) (FAC) versus FAC followed by high-dose chemotherapy (HDCT) and autologous stem cell support (ASCS) for patients with high-risk primary breast carcinoma. After a median follow-up of 6.5 years, no significant differences were observed in recurrence-free survival (RFS) or overall survival (OS) between the 2 arms. This report updates the survival analyses. Patients with >or=10 positive axillary lymph nodes after primary surgery or >or=4 positive lymph nodes at surgery after neoadjuvant chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were assigned randomly to receive either no further chemotherapy or 2 cycles of combined high-dose cyclophosphamide (5250 mg/m2 per cycle), etoposide (1200 mg/m2 per cycle), and cisplatin (165 mg/m2 per cycle) with ASCS. Primary endpoints were RFS and OS. RFS and OS were calculated by using the Kaplan-Meier method. The log-rank statistic was used to compare treatment arms. Between 1990 and 1997, 78 patients were registered, and 39 patients were assigned randomly to each arm. The median follow-up for all patients who were alive at last follow-up was 142.5 months (range, 45-169 months). An intention-to-treat analysis showed no significant difference between the 2 arms in terms of RFS (at 10 years: 40% with FAC vs. 26% with FAC plus HDCT; P=.11) or OS (at 10 years: 47% with FAC vs. 42% with FAC plus HDCT; P=.13). With a median follow-up of nearly 12 years for patients who remained alive, this trial continued to demonstrate no RFS or OS advantage for patients with high-risk primary breast carcinoma treated with HDCT after standard-dose FAC chemotherapy.

High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults

Since the early 1980s high dose chemotherapy with autologous hematopoietic stem cell support was adopted by many oncologists as a potentially curative option for solid tumors, supported by a strong rationale from laboratory studies and apparently convincing results of early phase II studies. As a result, the number and size of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) to prove or disprove its value was largely insufficient. In fact, with the possible exception of breast carcinoma, the benefit of a greater escalation of dose of chemotherapy with stem cell support in solid tumors is still unsettled and many oncologists believe that this approach should cease. In this article, we critically review and comment on the data from studies of high dose chemotherapy so far reported in adult patients with small cell lung cancer, ovarian cancer, germ cell tumors and sarcomas.

Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus

Manifestations of systemic lupus erythematosus (SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease. To assess the safety of intense immunosuppression and autologous hematopoietic stem cell support in patients with severe and treatment-refractory SLE. A single-arm trial of 50 patients with SLE refractory to standard immunosuppressive therapies and either organ- or life-threatening visceral involvement. Patients were enrolled from April 1997 through January 2005 in an autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) study at a single US medical center. Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (5 microg/kg per day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine antithymocyte globulin (90 mg/kg). The primary end point was survival, both overall and disease-free. Secondary end points included SLE Disease Activity Index (SLEDAI), serology (antinuclear antibody [ANA] and anti-double-stranded (ds) DNA), complement C3 and C4, and changes in renal and pulmonary organ function assessed before treatment and at 6 months, 12 months, and then yearly for 5 years. Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplantation for 4 months. Forty-eight patients underwent nonmyeloablative HSCT. Treatment-related mortality was 2% (1/50). By intention to treat, treatment-related mortality was 4% (2/50). With a mean follow-up of 29 months (range, 6 months to 7.5 years) for patients undergoing HSCT, overall 5-year survival was 84%, and probability of disease-free survival at 5 years following HSCT was 50%. Secondary analysis demonstrated stabilization of renal function and significant improvement in SLEDAI score, ANA, anti-ds DNA, complement, and carbon monoxide diffusion lung capacity adjusted for hemoglobin. In treatment-refractory SLE, autologous nonmyeloablative HSCT results in amelioration of disease activity, improvement in serologic markers, and either stabilization or reversal of organ dysfunction. These data are nonrandomized and thus preliminary, providing the foundation and justification for a definitive randomized trial. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00271934.

Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer

The objectives of this study were to investigate the tolerability of a novel high-dose chemotherapy (HDC) regimen with peripheral blood progenitor cell (PBPC) support in patients with pretreated advanced ovarian cancer and to determine the maximum-tolerated dose (MTD) of topotecan in this setting. Advanced ovarian cancer patients previously treated with platinum-based first-line therapy were enrolled. After PBPC mobilization and harvesting, patients received three consecutive cycles of HDC with PBPC support. Cycle 1 was carboplatin area under the concentration curve 20 and paclitaxel 250 mg/m(2). Cycle 2 was topotecan starting at 5 mg/m(2), dose escalated in 2 mg/m(2) increments, and etoposide 600 mg/m(2). Cycle 3 was thiotepa 500 mg/m(2). After each cycle, PBPCs were infused. Granulocyte colony stimulating factor (5 microg/kg/day) was administered until neutrophil recovery occurred. Seventeen patients were enrolled; all were safety evaluable. The most common nonhematologic toxicity was grade 3 mucositis (44%). Engraftment of PBPCs was successful in all patients after each cycle, and no treatment-related deaths occurred. Of 14 patients with measurable disease, 5 (36%) had complete responses, 2 (14%) had partial responses, and 4 (29%) had stable disease. The median progression-free and overall survivals were 7 and 18 months, respectively. The MTD of topotecan was not reached. The tolerability and activity of this regimen in patients with advanced ovarian cancer warrant further investigation.

Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer

Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer

Twelve-year follow-up of a randomized trial of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell support (ASCS) for high-risk primary breast carcinoma

663 Background: We previously reported on the results of a randomized trial of standard-dose chemotherapy with 5-fluorouracil, Adriamycin and cyclophosphamide (FAC) versus FAC followed by HDC and ASCS for high-risk primary breast cancer (J Natl Cancer Inst. 2000;92[3]:225–33). At a median follow-up of 6.5 years, no relapse-free (RFS) or overall survival (OS) advantage was seen between the two arms. Morbidity was increased with HDC. This report updates the survival analysis. Methods: Patients with ≥ 10 positive axillary nodes after primary surgery or ≥ 4 positive nodes at surgery following primary chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were stratified by stage, and randomly assigned to receive no further chemotherapy or 2 cycles of high-dose cyclophosphamide, etoposide, and cisplatin with ASCS. Primary endpoints were RFS and OS. Survival was calculated by the Kaplan-Meier method. The log-rank statistic was used to compare survival between treatment arms. Results: From 1990 to 1997, 78 patients were registered: 48 after primary surgery and 30 after primary chemotherapy. 39 patients were randomly assigned to FAC alone, and 39 to FAC followed by HDC. The median follow-up of live patients is 143 months (range 45 to 169 months). Detailed outcomes are shown in the table below. In intention-to-treat analysis, there was no significant difference in RFS (p = 0.114) or OS (p = 0.136) between the two groups by log-rank test. There have been no late toxicities since the last report. Conclusions: With 12 years of follow-up, this study continues to show no RFS or OS advantage associated with the use of HDC for high-risk primary breast carcinoma. No significant financial relationships to disclose.

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: First results of a randomized trial

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: First results of a randomized trial

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: First results of a randomized trial

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: First results of a randomized trial

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy.PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant.RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. [Display omitted] CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

Dose-dense chemotherapy in breast cancer and lymphoma

Adjuvant combination chemotherapy reduces the risk of relapse and death for patients with invasive breast cancer and adds to the benefits obtained with hormonal treatment. Generally, anthracycline-containing regimens are superior to non-anthracycline regimens, treatments longer than 6 months are not advantageous and high-dose chemotherapy regimens, which require autologous hematopoietic stem cell support, have not proved consistently superior. The development and evaluation of the taxanes was highly anticipated as they have shown high levels of efficacy while appearing to be non-cross-resistant with partially non-overlapping toxicities. A role for taxanes in the adjuvant or neoadjuvant setting is now widely acknowledged, although they are not currently approved for treatment of early breast cancer in Europe. In patients with aggressive lymphoma who receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, 40% to 70% of patients attain a complete remission, depending on risk factors such as age and extranodal involvement. Second- and third-generation regimens like m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide), Pro-MACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) have largely failed to improve treatment outcome. The use of monoclonal anti-CD20 antibodies or dose escalation have shown promising results in improving relapse-free and survival rates. In patients with breast cancer, the key Cancer and Leukemia Group B 9741 trial showed that dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy with granulocyte colony-stimulating factor (G-CSF), repeated every 2 weeks, is superior to the same regimen administered at standard 3-weekly intervals. In lymphoma, dose-dense CHOP chemotherapy has shown superiority over standard CHOP regimens, particularly in elderly patients with aggressive non-Hodgkin’s lymphoma. G-CSF factor is essential to enable the administration of dose-dense chemotherapy and any reduction in its use leads to significant increases in infectious complications. Current evidence suggests that dose-dense chemotherapy, enabled by G-CSF, is an important breakthrough in the evolution of chemotherapy for breast cancer and lymphoma.

Role for high-dose therapy with autologous hematopoietic stem cell support in Waldenstrom's macroglobulinemia

Despite effectiveness of standard chemotherapy regimens, complete responses are infrequent in Waldenstrom's macroglobulinemia (WM) and there are no cures. Since WM shares certain biological and clinical features with myeloma, including responsiveness to alkylating agents, evaluation of high-dose therapy (HDT) with transplant, which is effective in myeloma, is an obvious next step in an effort to achieve high response rates and improve survival. Due to the indolent nature of the disease and older patients with comorbidities, such evaluations have been infrequent in the past. We have evaluated the safety and efficacy of high-dose melphalan with peripheral blood stem cell (PBSC) support in eight patients between the ages of 45 and 69 years with WM. Adequate numbers of stem cells were collected in six patients; however, two patients with more extensive prior fludarabine therapy failed to collect adequate cells and required a second attempt at stem cell collection. Seven patients were treated with melphalan 200 mg/m 2, including two patients who received tandem transplants; one patient received melphalan 140 mg/m 2 with total body irradiation (TBI). There was no treatment-related mortality and toxicities were manageable. Recovery of bone marrow after transplant was prompt except in one patient with extensive prior use of fludarabine. All the eight patients achieved at least partial response (PR), including one complete response (CR). Five patients are alive and with out relapse (77+ to 6+ months post-transplant). Other investigators have reported similar experience suggesting safety and efficacy of HDT in WM. However, therapy with purine analogues leads to stem cell damage with decreased ability to collect adequate numbers of stem cells. This suggests that the PBSCs should preferably be procured prior to extensive use of purine analogues. Future strategies in WM will include a plan to evaluate the role of HDT along with biological agents, role of purging using rituximab, post-HDT maintenance strategies (including immunotherapy), and evaluation of nonmyeloablative regimens containing fludarabine to achieve higher response rates and improve survival. Semin Oncol 30:282-285. © 2003 Elsevier Inc. All rights reserved.

Breast Tumor Cell Contamination of Hematopoietic Stem Cell Collections

The survival for patients with advanced breast cancer following conventional combination chemotherapy remains limited. Attempts to circumvent drug resistance have involved high-dose chemotherapy along with autologous hematopoietic stem cell support. Despite this, relapse remains the primary cause of death. Breast tumor cells are commonly found in hematopoietic stem cell collections. The role of reinfused occult tumor cells in malignant relapse following high-dose chemotherapy has yet to be determined but is likely to have a negative impact. Strategies to decrease stem cell contamination under investigation include: (1) improved regimens for stem cell mobilization, (2) enhanced techniques for tumor cell detection, (3) targeted tumor cell purging and (4) alternative sources of stem cells. These approaches hold promise for improving the outcome of patients undergoing high-dose chemotherapy and stem cell reinfusion for poor-prognosis breast cancer.

Results of high-dose treatment with autologous stem cell support in patients with multiple myeloma

The introduction of high-dose treatment (HDT) with autologous hematopoietic stem cell support in patients with multiple myeloma (MM), although curative in only a minority of patients, has led to significantly longer event-free (EFS) and overall survival (OS) and likely improved quality of life compared with conventional chemotherapy. However, several issues remain unsettled. We review the current knowledge with respect to transplantation-related controversies, such as intensity of cytoreductive therapy (single v tandem transplants), optimal timing of the procedure, and potential benefit of graft purging and posttransplant consolidation chemotherapy. Special emphasis is placed on the safety and efficacy of transplant in elderly patients and in those with impaired renal function, who are usually excluded from the most effective therapy.

Brief Report Dexa-BEAM: An Effective Regimen for Cytoreduction Prior to High-Dose Chemotherapy with Autologous Stem Cell Support for Patients with Relapsed/Refractory Mantle-Cell Lymphema

Mantle-cell lymphoma (MCL) is not a curable disease using conventional chemotherapy. Patients with MCL have the shortest median time to progression and the shortest median survival of all lymphoma subtypes after first-line treatment. In the present study we determined the efficacy of maximal cytoreductive therapy with up to four cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell support (ASCT) for patients with advanced relapsed or refractory MCL. Nine consecutive patients with relapsed or refractory MCL were included. Three patients had partial remission (PR), three patients progressive disease (PD) upon first line tretment, and three patients first or subsequent relapse. After 2 to four cycles of Dexa-BEAM eight patients achieved complete remission (CR), resulting in a response rate of 88%. Six of 8 patients responding to Dexa-BEAM received high-dose chemotherapy HDCT (BEAM) and autologous hematopoietic stem cell transplantation (ASCT). With a median follow up of 24 months six patients are alive. Five of those six patients are still in contiuous CR (range 13–54 months).

Intense immune suppression for systemic lupus--the role of hematopoietic stem cells.

The treatment of severe autoimmune diseases has been recently revitalized by the introduction of intense immune suppression with immune ablative intent followed by three different procedures. These are allogeneic hematopoietic stem cell transplantation (HSCT), autologous HSCT (using either marrow or peripheral blood), and intense immune suppression without stem cell support. Current trials suggest that high dose immune suppressive therapy with or without autologous hematopoietic stem cell support can induce remission of previously refractory disease. Follow-up is too brief to determine if intense immune suppression, and more specifically autologous HSCT, will ultimately cure SLE. It is conceivable that an allogeneic source of stem cells from a normal donor (e.g. HLA matched sibling) will be required to achieve a cure. It is also possible that autologous HSCT, even if not curative, may prolong the life of patients with otherwise high-risk features. In carefully selected patients, the potential benefits of this procedure may outweigh the risks.

Autotransplants in men with breast cancer. ABMTR Breast Cancer Working Committee. Autologous Blood and Marrow Transplant Registry.

The purpose of this study was to determine the outcome of high-dose therapy with autologous hematopoietic stem cell support (autotransplants) in men with breast cancer. We studied 13 men receiving autotransplants for breast cancer and reported to the Autologous Blood and Marrow Transplant Registry (ABMTR) by 10 centers. Six men had stage 2 breast cancer, four had stage 3, and three had metastatic breast cancer. Of twelve tumors tested, all were estrogen receptor positive. Median age at transplant was 50 years. The most common conditioning regimen was cyclophosphamide, thiotepa and carboplatin (n = 5); the remaining eight men received other alkylator-based regimens. Three men received bone marrow, eight received blood stem cells, and two received both for hematopoietic support. All patients had hematopoietic recovery. There were no unexpected regimen-related toxicities. Of 10 men receiving autotransplants as adjuvant therapy, three relapsed 3, 5 and 50 months post-transplant and died 16, 19 and 67 months post-transplant. Seven of 10 are disease-free with median follow-up of 23 months (range 6-50 months). Of three men treated for metastatic breast cancer, one had progressive disease and two recurrent disease at 6, 7 and 16 months post-transplant. In conclusion, results of autotransplants for male breast cancer appear similar to those reported for women receiving autotransplants for breast cancer.