Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma

BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL). METHODS: This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%). RESULTS: After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days. CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.     

Sequential high-dose therapy and autologous stem cell transplantation for treatment of mantle cell lymphoma

Background: Mantle cell lymphoma (MC) is not curable with conventionalchemotherapy. To improve the prognosis of patients with this disease, weprospectively studied an intensive sequential therapy consisting of theDexa-BEAM regimen (dexamethasone, BCNU, etoposide, ara-C, melphalan) followedby myeloablative therapy with autologous stem cell reinfusion.Patients and methods: Nine consecutive patients with stage III/IV MC wereincluded. Two had untreated disease, four were in first remission, whereasthree had more advanced disease. All patients underwent one to two cycles ofDexa-BEAM chemotherapy to reduce the tumor load and to mobilize peripheralblood progenitor cells (PBPC). Subsequently, patients were treated withhigh-dose radiochemotherapy followed by PBPC reinfusion and were prospectivelyanalyzed for residual disease by clinical methods as well as by PCRamplification clonal CDRIII rearrangements.Results: With an overall response rate of 100%, the initialDexa-BEAM cycles effectively reduced the tumor load. All patients proceededto high-dose therapy and subsequent stem cell rescue. Engraftment was prompt,and procedure-related deaths did not occur. With a median follow-up of 12(3–33) months post transplant, all patients are alive in continuingclinical and molecular remission.Conclusions: Sequential intensive therapy consisting of Dexa-BEAM andhigh-dose radiochemotherapy appears to be a highly effective treatment forpatients with MC. However, the data are still preliminary, and larger patientnumbers and a longer follow-up are required.     

The role of high-dose therapy and autologous hematopoietic stem cell transplantation for mantle cell lymphoma

Background: Although mantle cell lymphoma (MCL) is a distinctdisease entity with well described clinical and pathologicalfeatures, little information exists regarding its therapy. Thispaper will evaluate patients with MCLreceiving either inductiontherapy with an anthracycline or high-dose chemotherapy andautologous hematopoietic stem cell transplantation for relapseddisease. Patients and methods: The cases of 14 previously untreated patientswith MCL who received an anthracycline-containing combinationchemotherapy regimen on Nebraska Lymphoma Study Group protocolsfrom 3/83 to 2/92 were reviewed. During the same time period,a different set of nine patients with recurrent MCL were referredfor high-dose chemoradiotherapy and autologous stem cell rescueas salvage therapy. Results: The five year overall (OS) and failure-free (FFS) survivalsfrom the initiation of chemotherapy for the patients receivingan induction therapy with an anthracycline containing regimenwere 23% and 8%, respectively. At the time of this analysis,three of the nine transplant patients remain progression-free7, 12, and 25 months post-transplant. Two year overall and FFSfor all nine patients was 34%. Conclusions: Longer follow-up of greater patient numbers isrequired to determine whether high-dose therapy can overcomethe chemoresistance and increase the cure rate of MCL. Sincemost patients with this disease have minimal chance of curewith standard chemotherapy, the optimal timing for high dosetherapy may be as part of front-line treatment. Further clinicaltrials are required to investigate the potential benefits ofhigh-dose therapy for patients with MCL. mantle cell lymphoma, hematopoietic stem cell transplantation     

Investigational strategies in autologous stem cell transplantation for follicular lymphoma

Recent retrospective analyses indicate prolonged survival for patients with follicular lymphoma over the past 25 years, attributed most likely to improved supportive care and sequential application of effective therapies. Encouraging results were obtained from several randomized trials evaluating myeloablative therapy followed by autologous stem cell transplantation (ASCT) as consolidation therapy applied to patients with advanced-stage follicular lymphoma either in first remission or as salvage therapy. However, because of the successful introduction of rituximab to the standard therapeutic repertoire, with its long-term beneficial clinical impact, ASCT must be reevaluated in prospective clinical trials, especially taking into account the potential short- and long-term toxicity associated with high-dose therapy. The concept of in vivo purging before or after ASCT and the introduction of radioimmunotherapy as part of the myeloablative regimen may further improve treatment results, reduce toxicity, and increase applicability. Combination of these novel strategies into a multimodal approach justifies hope that the treatment outcome of patients suffering from follicular lymphoma will be further improved.     

T淋巴母细胞淋巴瘤自体干细胞移植后的长期随访观察

目的评价自体造血干细胞移植(autologous hematopoietic stem cell transplantation,AHSCT)治疗复发难治T淋巴母细胞淋巴瘤(TLBL)的临床疗效及安全性。方法本文回顾性分析AHSCT治疗后长期随访的TLBL16例,预处理方案主要为BEAM和BEAC。结果 15例患者可评价疗效,1例失访。中位随访37个月(12~132个月),中位无进展生存时间(PFS)34.5个月。预计中位总生存时间49月。1、3、5年总生存率分别为60%、53%、32%。初治患者一线治疗有效者,接受AHSCT者预计中位总生存时间为108个月,5年总生存率、无进展生存率分别为62%、63%;复发患者挽救治疗后接受AHSCT者,中位总生存时间为22.8个月,5年总生存率、无进展生存率分别为33%、22%。初始治疗未达CR/PR的难治患者,中位生存仅21个月,5年生存率和无进展生存率分别为20%和29%。结论 AHSCT常规化疗治疗TLBL安全、有效,可提高复发难治的T淋巴母细胞淋巴瘤的远期生存,延长初治TLBL患者的无进展生存期,但复发率仍偏高,值得开展大规模临床试验进一步深入研究。     

T淋巴母细胞淋巴瘤自体干细胞移植后的长期随访观察

目的评价自体造血干细胞移植（autologous hematopoietic stem cell transplantation,AHSCT）治疗复发难治T淋巴母细胞淋巴瘤（TLBL）的临床疗效及安全性。方法本文回顾性分析AHSCT治疗后长期随访的TLBL16例,预处理方案主要为BEAM和BEAC。结果 15例患者可评价疗效,1例失访。中位随访37个月（12~132个月）,中位无进展生存时间（PFS）34.5个月。预计中位总生存时间49月。1、3、5年总生存率分别为60%、53%、32%。初治患者一线治疗有效者,接受AHSCT者预计中位总生存时间为108个月,5年总生存率、无进展生存率分别为62%、63%;复发患者挽救治疗后接受AHSCT者,中位总生存时间为22.8个月,5年总生存率、无进展生存率分别为33%、22%。初始治疗未达CR/PR的难治患者,中位生存仅21个月,5年生存率和无进展生存率分别为20%和29%。结论 AHSCT常规化疗治疗TLBL安全、有效,可提高复发难治的T淋巴母细胞淋巴瘤的远期生存,延长初治TLBL患者的无进展生存期,但复发率仍偏高,值得开展大规模临床试验进一步深入研究。     

Engraftment and outcomes following autologous stem cell transplantation in Hodgkin lymphoma patients mobilized with plerixafor

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non‐Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long‐term post‐transplant outcomes in patients transplanted with plerixafor‐mobilized PBSCs are lacking. This retrospective study examined the post‐transplant outcomes of 105 consecutive adult HL patients, and compared the post‐transplant outcomes of 21 patients who received plerixafor in addition to G‐CSF ± chemotherapy because of poor mobilization with those of 84 patients who mobilized well without plerixafor. Despite collecting significantly lower CD34+ cell doses (median of 3.41 vs. 6.05 × 10⁶/kg, p < 0.0001) than control patients and requiring more collection days, plerixafor‐mobilized patients showed comparable early engraftment characteristics, except for slightly delayed neutrophil engraftment (median: 11 vs.10 days, p = 0.002) and lower median neutrophil counts (2.1 vs. 2.6 × 10⁹/L, p = 0.04) at one month after transplant. No significant differences were observed in longer term post‐transplant outcomes, including cell counts at 3, 6, and 12 months, RBC and platelet transfusion support during the first 120 days, relapse incidence, overall and progression‐free survival rates up to two years post transplant. The use of plerixafor not only enabled poorly mobilizing HL patients to collect enough PBSCs to proceed to ASCT, but also to have similar post‐transplant outcomes compared to patients who mobilized well with conventional regimens. Copyright © 2016 John Wiley & Sons, Ltd.     

An update on the role of high-dose therapy with autologous or allogeneic stem cell transplantation in mantle cell lymphoma

PURPOSE OF REVIEW: Early trials of high-dose therapy with autologous stem cell transplantation in mantle cell lymphoma were discouraging, with no clear survival advantage attributable to the procedure. Most early series were plagued by small numbers, retrospective designs, and short follow-up. Also, until recently, allogeneic stem cell transplantation was not an option for most mantle cell lymphoma patients who were too old or infirm to tolerate standard conditioning regimens. RECENT FINDINGS: New advances in allogeneic transplantation, particularly reduced-intensity conditioning regimens, have increased the availability of this procedure to patients with mantle cell lymphoma. New evidence has emerged during the last several years that suggests autologous stem cell transplantation in first complete remission may provide a survival advantage over conventional chemotherapy in patients with mantle cell lymphoma. Additionally, investigational strategies such as in vivo purging with rituximab and the use of radioimmunotherapy in conditioning regimens may further increase response rates and, hopefully, survival in mantle cell lymphoma patients. Finally, recent studies suggest the existence of a graft-versus-lymphoma effect in mantle cell lymphoma providing strong scientific rationale for the possible curative potential of allogeneic stem cell transplantation in this disease. SUMMARY: This review focuses on recent advances in allogeneic and autologous transplantation for mantle cell lymphoma. Particular emphasis is placed on the role of autologous transplantation in first complete remission, the role of in vivo purging with rituximab, the utility of radioimmunotherapy and, finally, the evolving strategy of reduced-intensity allogeneic stem cell transplantation.     

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.     

Negative immunomagnetic ex vivo purging combined with high-dose chemotherapy with peripheral blood progenitor cell autograft in follicular lymphoma patients: evidence for long-term clinical and molecular remissions.

The feasibility and efficacy of a novel immunomagnetic ex vivo negative purging method was evaluated on peripheral blood progenitor cells (PBPC) from 13 non-Hodgkin's lymphoma patients (eight follicular, FL; three mantle cell, MCL; two FL with histologic transformation). A peculiar feature of the study was the collection of PBPC after prolonged tumor debulking. Our method included a stem cell enrichment phase followed by cell incubation with anti-B cell MoAbs (anti-CD19, CD20, CD22, CD23), addition of immunobeads, and then positive cell removal by passage on a Max-Sep (Baxter Immunotherapy) cell separator. Engraftment was rapid and stable. Hematological values were assessed 1 and 2 years after the autograft. Purging efficacy was molecularly assessed in a panel of 11 patients who showed persistence of PCR-detectable lymphoma cells on PBPC harvests despite intensified chemotherapeutic debulking. PCR-negativity was obtained in vitro and persisted in vivo after autograft in three FL patients; five more FL patients, whose purged PBPC were PCR+, converted to stable (3 patients) or fluctuating (two patients) PCR negativity after autograft. MCL patients never reached PCR negativity. Thus, ex vivo purging may have a role for FL patients harvesting PCR-positive PBPC after intensified chemotherapy. In contrast, the addition of ex vivo purging seems to be of little if any benefit for MCL patients.     

High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤59例回顾性分析

目的:通过分析大剂量化疗(HDT)联合自体造血干细胞移植(ASCT)治疗淋巴瘤的临床体会,探究安全合理的动员和预处理方案,以进一步提高治疗的安全性和疗效.方法:对59例接受HDT联合ASCT治疗的淋巴瘤患者的资料进行回顾分析.结果:59例患者采集到足够数量的造血干细胞,预处理后接受ASCT并成功恢复造血.随访1～88个月(中位数26.3个月),47例患者无病生存1～88个月(中位数28.5个月),10例在移植后2～37个月死于肿瘤复发,1例移植后16个月死于深部霉菌感染.1例移植后9个月死于爆发性肝炎.结论:HDT联合ASCT与常规化疗有机结合可能是治疗淋巴瘤安全、有效的方法.     

Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma

BackgroundHigh-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined.Patients and methodsIn this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation.ResultsMR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24–0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23–0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed.ConclusionsThese data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.     

Phase I trial of (90)Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation

Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT.     

Effectiveness of high-dose polychemotherapy and autologous hemopoietic cell transplantation in patients with low-grade non-Hodgkin lymphoma

The study included 70 patients with high-grade malignant non-Hodgkin's lymphoma (Kiel) who received the following treatment: group 1(24)--6-8 cycles of CHOP; group 2 (relapse or tumor progression after standard chemotherapy--13)--6 cycles of CHOP and Dexa-BEAM, and group 3 (relapse or tumor progression after standard chemotherapy--8)--6 cycles of CHOP plus Dexa-BEAM plus autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells). The groups were comparable as far as gender and age are concerned. Overall 5-year survival rates were 81, 20 and 48%, respectively. CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to CHOP-Dexa-BEAM alone.     

Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as 'in vivo purge' and consolidative immunotherapy following autologous stem cell transplantation.

BACKGROUND: Little is known about the pharmacokinetics of rituximab in an autologous stem cell transplant (ASCT) setting. PATIENTS AND METHODS: We evaluated serum rituximab levels in 26 patients with follicular or mantle cell lymphoma treated with a combination of ASCT and immunotherapy. Patients received nine infusions of rituximab (375 mg/m(2)): one dose as an 'in vivo purge' prior to stem cell collection, and two 4-week cycles at 8 and 24 weeks following ASCT. Pre- and post-infusion serum rituximab levels were measured during the purging dose, with doses 1 and 4 of both sets of maintenance rituximab cycles, and 12 weeks and 24 weeks following treatment. RESULTS: Rituximab levels were detectable after the first infusion, and peaked at a mean concentration of 463.8 micro g/ml after the final dose. Levels remained detectable 24 weeks after completion of treatment. There was a trend toward higher rituximab levels in patients with follicular lymphoma. Serum concentrations achieved during the maintenance cycles were similar to levels observed in patients with measurable lymphoma treated during 'the pivotal trial'. No correlation was observed between serum rituximab levels achieved in the minimal disease state and the risk of later clinical relapse, nor with the ability to achieve a molecular remission following ASCT. CONCLUSIONS: The finding that patients treated in minimal disease states and at the time of active disease both achieve similar final serum rituximab concentrations after four infusions suggests that the pharmacokinetics are complex, and may not necessarily correlate with disease burden. The precise factors influencing rituximab clearance in patients with lymphoma are unresolved, and this remains an area of active research.     

非霍奇金淋巴瘤自体外周血干细胞中肿瘤污染的临床研究

目的：了解非霍奇金淋巴瘤（NHL）患者自体外周血干细胞（APBSC）移植物中肿瘤细胞污染的情况,探讨移植物被肿瘤细胞污染对预后的影响。方法：以免疫球蛋白重链（IgH),T细胞受体γ（TCRγ）基因克隆性重排和BCL－2/IgH融合基因为检测标志,应用PCR结合SSCP技术检测了33例NHL患者APBSC标本中的微量肿瘤细胞,同时还检测了部分患者自体外周血干细胞移植（APBSCT）前后骨髓中的微量肿瘤细胞,结果：8例（24．2％）患者的17份（23．6％）APBSC标本微量肿瘤细胞检测阳性,动员时骨髓微量肿瘤细胞检测为阳性和阴性的患者,其APBSC污染阳性率分别为66．7％（6／9）和8．7（2／23）,二者差异有显著性（P＜0．01）,APBSC污染阳性和阴性患者的移植后预期3年总生存率分别为71．4％和71．2％,预期3年无病生存率分别为25．0％和61．5％,结论：NHL患者采集的APBSC可受到肿瘤细胞的污染,APBSC动员时骨髓微量肿瘤细胞阳性增加APBSC污染的几率。     

Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

The aim of this prospective, single-arm study was to test the efficacy and tolerability of autologous stem cell transplantation (auto-SCT) combined with in vivo rituximab purging and post-transplant rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL). This study included 12 DLBCL patients aged 18-65 years with an International Prognostic Index ≥2. The patients received 4-6 cycles of induction therapy consisting of rituximab plus cyclophosphamide, adriamycin, vincristine and prednisone followed by salvage therapy prior to stem cell mobilization. This regimen was followed by rituximab maintenance therapy (375 mg/m(2) every three months for two years). Prior to auto-SCT, six patients (50%) achieved complete remission (CR) and six (50%) achieved unconfirmed complete remission (CRu). Three months after transplantation, 11 patients (91.7%) achieved CR and one achieved CRu. After two cycles of rituximab maintenance therapy, all 12 patients achieved CR. Long-term CR was achieved by 10 patients, while two experienced relapse at 14 and 20 months after the end of rituximab maintenance therapy. The median follow-up period was 44 months (range 35-61). Disease-free survival was noted in 10 patients, while two experienced relapse. The three-year overall survival (OS) and progression-free survival (PFS) were 100 and 83%, respectively. Prolonged hypogammaglobulinemia occurred in two patients, although no increase in major infections was observed. Hepatitis B surface antigen was continuously negative in all 12 patients. Our results demonstrated that auto-SCT combined with in vivo rituximab purging and post-transplant rituximab maintenance is safe and effective, and may extend OS and PFS in younger high-risk DLBCL patients.     

Nonmyeloablative stem cell transplantation in follicular B-cell lymphoma

Myeloablative allogeneic stem cell transplantation carries the promise of long-term disease control by graft-versus-lymphoma (GVL) immunity but is associated with a 30% to 40% risk of transplant-related mortality. Nonmyeloablative stem cell transplantation (NST) aims to exploit the GVL effect without the attendant toxicity of myeloablative conditioning. At the M.D. Anderson Cancer Center, the standard NST conditioning regimen for patients with follicular lymphoma is fludarabine, cyclophosphamide, and rituximab (FCR). Using this regimen, transplant-related mortality is currently 10%, and 85% of patients remain alive without disease at 3 to 4 years. This review discusses the current issues in NST for follicular lymphomas, including the optimization of conditioning intensity, the use of rituximab in immunomodulation, and the role of donor lymphocyte infusion.