Clinical observation of FMD regimen: Fludarabine,mitoxantrone, dexamethasone,in treatment of non-Hodgkin’s lymphoma

Objective

To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma.

Methods

Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25～30 mg/m² days 1～3, mitoxantrone 8～10 mg/m² day 1, and dexamethasone 20～30 mg/m² days 1～5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin.

Results

Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3～4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3～4 thrombocytopenia. At a median follow-up of 24 (5～54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.

Conclusion

FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.

     

Phase II study of 9-aminocamptothecin in previously treated lymphomas: results of Cancer and Leukemia Group B 9551

Purpose  To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods  Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin’s lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m² per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m² per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results  CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion  Single agent 9-AC has modest activity in aggressive non-Hodgkin’s lymphomas.     

氟达拉滨联合方案治疗复发难治非霍奇金淋巴瘤临床疗效观察

目的观察氟达拉滨联合化疗治疗复发难治非霍奇金淋巴瘤临床疗效及安全性。方法38例复发难治非霍奇金淋巴瘤患者均采用FND方案：氟达拉滨30mg/m² d1~3,米托蒽醌10mg/m² d1,曲安西龙80mg pod 1~5, 28天一周期。结果全组患者CR 8例（21%）,PR 13例（34%）,有效率56%;其中20例复发难治惰性淋巴瘤患者CR7例（35%）,PR9例（45%）,有效率80%; 18例复发难治侵袭性淋巴瘤患者CR 1例（6%）,PR 4例（22%）,有效率28%（ χ²=10.45, P =0.001）。全组患者中位随访22（1~47）月,复发难治惰性淋巴瘤患者中位生存期45（2~47）月,中位无进展生存期18（2~34）月;复发难治侵袭性淋巴瘤患者中位生存期15（2~45）月,中位无进展生存期3（1~22）月。不良反应主要为骨髓抑制和肺感染。结论氟达拉滨联合方案治疗惰性淋巴瘤疗效肯定,对复发难治侵袭性淋巴瘤患者疗效尚可,不失为一种治疗选择。     

Efficacy and safety of the combination of rituximab,fludarabine, and mitoxantrone for rituximab‐naive,recurrent/refractory follicular non‐Hodgkin lymphoma with high tumor burden

BACKGROUND:

This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R‐FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.

METHODS:

Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP‐like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion >7cm), 56% had high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3‐5), and 22% were refractory. Treatment consisted of 4 courses of R‐FM (rituximab 375 mg/m² intravenously on Day 1, fludarabine 25 mg/m² intravenously on Days 2 through 4, and mitoxantrone 10 mg/m² intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab).

RESULTS:

The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R‐FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow‐up of 4 years, the 3‐year progression‐free survival rate was 47%, the event‐free survival rate was 41%, and the 3‐year overall survival rate was 66%. Grade ≥3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively.

CONCLUSIONS:

Cytoreduction with 4 courses of R‐FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome. Cancer 2010. © 2010 American Cancer Society.     

Excellent Tolerance of Rituximab When Given After Mitoxantrone/Cyclophosphamide: An Effective and Safe Combination for Indolent Non-Hodgkin's Lymphoma

Treatment for extensive indolent lymphoma should provide optimization of efficacy while avoiding excessive toxicity. Rituximab may be an ideal agent to combine with chemotherapy because of its lack of classical myelotoxicity. In this study, 27 patients with a variety of histologies of indolent B-cell non-Hodgkin's lymphoma have been treated utilizing a novel three-drug combination. Nine patients had relapsed disease and 18 were previously untreated. Patients first received cyclophosphamide 800 mg/m² and mitoxantrone 8 mg/m² I.V. on day 1, every 3 weeks for 2 cycles. Subsequently, patients received rituximab 375 mg/m² followed by mitoxantrone 8 mg/m² every 2 weeks for 4 cycles. This regimen and, in particular, the rituximab infusion were extremely well tolerated. Only two of 27 patients experienced a grade 1/2, infusion-related reaction during the first rituximab infusion. Grade 4 neutropenia was noted at some point in 16 patients who were then offered granulocyte-macrophage colony-stimulating factor support for improvement of neutropenia. No infections were noted. Alopecia was minimal. Of 27 patients, 19 achieved a complete response (CR), one achieved an unconfirmed CR (CRu), and five patients achieved a partial response, for an overall response rate of 92.5%. Molecular remissions were noted in seven of 12 tested patients in CR. We concluded that the cyclophosphamide/mitoxantrone/rituximab (CyMiR) regimen is effective and extremely well tolerated. Furthermore, rituximab infusion-associated morbidity is markedly reduced .     

含美罗华方案治疗B细胞性惰性淋巴瘤34例报告

背景与目的：国外临床研究证实利妥昔单抗（rituximab,商品名美罗华）无论是单药还是与化疗药物联用治疗初治或复发惰性淋巴瘤均取得较好疗效。本研究目的是观察含美罗华方案治疗我国惰性淋巴瘤的疗效和安全性。方法：从1999年3月到2005年1月．共34例经病理确诊的惰性淋巴瘤患者接受含美罗华的方案化疗,中位疗程数5个（3～8个）,单药治疗2例．联合化疗32例。化疗方案包括CHOP16例、FMD5例、CHOPE4例、EPOCH2例、DICE2例、DAHP2例和FN1例。结果：34例患者中30例可评价疗效,总有效（OR）率为93-3％,完全缓解（CR）率为60．0％;22例初治患者可评价疗效,OR率95．4％,CR率66．7％;18例滤泡淋巴瘤患者可评价疗效,OR率为88．9％,CR率为66．7％。中位随访期17个月（4～68个月）．1年无疾病进展生存（progression-freely survival,PFS）率为85-3％。主要不良反应为骨髓抑制,19例患者出现白细胞下降,5例患者血小板下降,其中Ⅲ＋Ⅳ度白细胞和血小板下降4例,2例出现中性粒细胞减少性发热;其它不良反应包括Ⅰ～Ⅱ度恶心呕吐、轻度脱发和肝功能受损等。美罗华输注相关不良反应有Ⅰ～Ⅱ度寒战和发热（发生率20．5％）、皮疹、轻度血压下降和无症状性室性早搏等。结论：美罗华单药或联合化疗治疗惰性淋巴瘤具有良好的临床疗效和安全性。     

A multicenter,phase II study of R-THP-COP therapy for elderly patients with newly diagnosed,advanced-stage,indolent B-cell lymphoma

The optimal combined chemotherapy regimen with rituximab has yet to be established for elderly patients with advanced-stage indolent B-cell lymphoma (B-NHL). A multicenter study was performed to evaluate the efficacy and toxicity of R-THP-COP therapy in elderly patients (aged 70–79 years) with newly diagnosed advanced-stage indolent B-NHL using the complete response rate (%CR) as the primary endpoint. Patients with newly diagnosed, clinical stage III/IV, indolent B-NHL, aged 70–79 years, with a performance status of 0–2 were eligible for this study. R-THP-COP consists of 375 mg/m² of rituximab, 50 mg/m² of pirarubicin, 750 mg/m² of cyclophosphamide, 1.4 mg/m² of vincristine, and 100 mg/day of oral prednisolone for 5 days. This study was discontinued due to poor accrual after the enrollment of 18 patients, although the planned sample size was 40 patients. The numbers of patients with follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, and mantle cell lymphoma were 16, 1, and 1, respectively. The median age was 73 (range, 70 to 79) years. The %CR including unconfirmed CR was 45% (95% confidence interval: 25-66%) and the overall response rate was 72%. The estimated 5-year overall survival and progression-free survival rates were 55% and 28%, respectively. The major toxicity observed was grade 4 neutropenia (94%). Grade 4 non-hematological toxicities were not observed and no patients developed grade 3/4 cardiac toxicities. This phase II study provides useful information regarding the efficacy and toxicity of R-THP-COP therapy for patients aged 70 years or older with newly diagnosed, advanced-stage, indolent B-NHL, although the sample size was small.     

Safety and efficacy of combination therapy with fludarabine, mitoxantrone, and rituximab followed by yttrium-90 ibritumomab tiuxetan and maintenance rituximab as front-line therapy for patients with follicular or marginal zone lymphoma

BackgroundWe conducted a single-institution phase II clinical trial evaluating the safety and efficacy of combination chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance as front-line treatment in indolent lymphomas.Patients and MethodsWe enrolled 20 patients with intermediate- to high-risk follicular lymphoma and 2 patients with marginal zone lymphoma. Treatment consisted of 4-6 cycles of FM (fludarabine 25 mg/m² on days 1-3, mitoxantrone 12 mg/m² on day 1 of each 28-day cycle). The protocol was amended after enrolling the first 4 patients to include rituximab 375 mg/m² on day 1. After 6-8 weeks, responders received ⁹⁰Y-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m² weekly × 4 doses, repeated every 6 months for 2 years).ResultsAfter R-FM, the overall response rate was 95% with a complete response rate (CR) of 45% (n = 10), a partial response (PR) rate of 50% (n = 11), and stable disease in 1 patient. Nineteen patients received ⁹⁰Y-ibritumomab tiuxetan with a 60% conversion rate of PR to CR, resulting in an improved CR of 79% (n = 15) and a PR of 21% (n = 4). Fifteen patients proceeded to rituximab maintenance resulting in 3 patients with PR converting to CR. At median follow-up of 49.6 months, median progression-free survival (PFS) was 47.2 months and median overall survival (OS) was not reached in an intent-to-treat analysis. The most common adverse effects were hematologic, with 2 patients experiencing treatment-related myelodysplastic syndrome (MDS), evolving to acute myelogenous leukemia (AML) in 1 patient.ConclusionR-FM with ⁹⁰Y-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.     

Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: phase 1 study with a dose-expansion cohort

BACKGROUND:

Pixantrone dimaleate (pixantrone) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models. FND‐R, a combination regimen of fludarabine, mitoxantrone, dexamethasone, and rituximab, has been shown to be an effective regimen for low‐grade lymphomas.

METHODS:

This dose‐escalation study, with an expansion cohort, was conducted to evaluate the safety and preliminary efficacy of FPD‐R, in which pixantrone was substituted for mitoxantrone in the FND‐R regimen, in patients with relapsed or refractory indolent non‐Hodgkin lymphoma (NHL). Escalated doses of pixantrone were administered to newly enrolled patients on day 2 of each 28‐day cycle of FPD‐R.

RESULTS:

Twenty‐eight of 29 enrolled patients received at least 1 cycle of FPD‐R (median, 5 cycles). Pixantrone 120 mg/m² was identified as the recommended dose in this regimen. Grade 3‐4 adverse events were primarily hematologic; grade 3‐4 lymphopenia occurred in 89% of patients and leukopenia in 79%. No patients developed congestive heart failure or grade 3‐4 cardiac adverse events. Left ventricular ejection fraction decreases occurred in 8 (29%) patients, and most were grade 1 or 2, transient, and asymptomatic. The overall response rate was 89%. Estimated survival was 96% after 1 year and 92% after 3 years.

CONCLUSIONS:

The FPD‐R regimen was well‐tolerated and highly active in patients with relapsed or refractory indolent NHL. Cancer 2011;. © 2011 American Cancer Society.     

氟达拉滨联合方案治疗恶性淋巴瘤的临床疗效

背景与目的：氟达拉滨是抗病毒药阿糖腺苷的氟化核苷酸类似物，用于治疗慢性淋巴细胞性白血病和复发耐药的惰性淋巴瘤已显示了疗效。本研究的目的为评价氟达拉滨联合方案治疗恶性淋巴瘤的疗效和安全性。方法：2004年1月至2005年11月间本科收治经组织学确诊的接受含氟达拉滨联合化疗的恶性淋巴瘤患者共19例，其中惰性淋巴瘤患者11例，复发的进展性淋巴瘤患者8例。11例惰性淋巴瘤患者中，6例接受了FND（氟达拉滨25mg／m^2Ⅳ d1-3；米托葸醌10mg／m^2Ⅳ d1；地塞米松20mgPOd1～5，每4周重复）方案，5例接受了FC（氟达拉滨25mg／m^2Ⅳ d1-3；环磷酰胺300mg／m^2Ⅳ d1-3，每4周重复）方案。所有进展性淋巴瘤患者均接受了FND方案。结果：接受FND或FC化疗的惰性淋巴瘤患者，有效率91％，完全缓解（CR）率45．5％。进展性淋巴瘤息者中2例达部分缓解（PR），有效率25％。全组有效率63．1％。主要不良反应为骨髓抑制。FND组有69．5％周期发生Ⅲ／Ⅳ度中性粒细胞减少。FC组无Ⅳ度中性粒细胞减少，仅22．2％周期发生Ⅲ度中性粒细胞减少。发生肺部感染4例，外阴尖锐湿疣1例。其他不良反应均为轻度，以消化道反应为主。结论：含氟达拉滨的联合方案，对于惰性淋巴瘤患者具有肯定的疗效，不良反应可以耐受。     

Initial experience with bendamustine in patients with recurrent primary central nervous system lymphoma: a case report

Novel therapeutic options for patients with recurrent primary central nervous system lymphoma (RPCNSL) are needed. Bendamustine, a bifunctional purine analog/alkylating agent, is approved for use in patients with progressive systemic indolent non-Hodgkin’s B-cell lymphomas. Limited data suggests that bendamustine may partition into the brain in the setting of a disrupted blood–brain barrier. This report describes the first known experience of patients with RPCNSL treated with bendamustine. Therapy was well-tolerated and best response was noted as stable disease after eight cycles of bendamustine followed by a subsequent local systemic recurrence found at five months follow-up. CNS involvement in this patient remained stable 20 + months post-bendamustine treatment. Based on our observations, further neuropharmacokinetic and efficacy studies with bendamustine may be warranted in this patient population.     

氟达拉滨联合米托蒽醌、地塞米松治疗惰性淋巴瘤疗效分析

目的比较氟达拉滨（FLU）联合米托蒽醌（MIT）、地塞米松（DXM）（FMD方案）与CHOP方案治疗惰性淋巴瘤的疗效。方法73例初、复治惰性淋巴瘤病人分3组。A组：FMD初治组；B组：FMD复治组；C组：CHOP方案治疗组。结果A组的CR率为59．1％，高于B组的CR率28．6％（P〈0．05），A组的总有效率（CR＋PR）86.4％，高于B组的总有效率（CR＋PR）57．1％（P〈0．05）。A组的CR率亦高于C组的CR率26．6％（P〈0．025），A组总有效率高于C组的总有效率63.3％，但差异不显著（P〉0．05）。结论初治惰性淋巴瘤病人采用FMD方案疗效优于复治病人；初治惰性淋巴瘤病人采用FMD方案疗效优于CHOP方案。     

氟达拉滨为主的联合化疗方案治疗低度恶性非霍奇金淋巴瘤的临床观察

目的评价以氟达拉滨为主的化疗方案治疗低度恶性淋巴瘤的疗效和不良反应。方法采用氟达拉滨为主的化疗方案(FMD方案:氟达拉滨 米托蒽醌 地塞米松;FMC方案:氟达拉滨 米托蒽醌 环磷酰胺;FC方案:氟达拉滨 环磷酰胺)治疗我院收治的低度恶性非霍奇金淋巴瘤患者32例,其中初发19例,复发、难治13例。结果32例患者平均完成了4.1个疗程,完全缓解(CR)率为65.6%,部分缓解(PR)率为18.8%,总的有效(OR)率为84.4%。初发组CR率71.4%, PR率21.0%,OR率92.4%;复发、难治组CR率46.2%,PR率13.1%,OR率59.3%,两组CR率和OR率差异无统计学意义(P>0.05)。主要不良反应为骨髓抑制和免疫功能抑制。31.3%(10/32)的患者出现Ⅲ～Ⅳ级粒细胞减少,9.4%(3/32)的患者出现Ⅲ～Ⅳ级血小板减少。有7例患者出现感染、发热,其中2例肺部感染患者死亡。非血液学毒性主要为胃肠道反应及轻度的肝肾功能损害。中位随访时间16个月(1～30个月),2年总生存(OS)率(93.8±4.2)%,2年疾病无进展生存(PFS)率(84.4±6.3)%。初发组2年OS率为100%,2年PFS率为(94.7±5.0)%;复发、难治组2年OS率为(76.9±11.3)%,2年PFS率为(69.2±12.3)%,两组差异无统计学意义(P>0.05)。结论氟达拉滨为主的化疗方案患者耐受性较好,对低度恶性淋巴瘤疗效较好,有可能改善患者的预后。     

New developments in immunotherapy for non-Hodgkin’s lymphoma

The clinical development of immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody) has markedly affected the treatment approach for patients with B-cell non-Hodgkin’s lymphoma (NHL). Rituximab was initially evaluated in relapsed indolent lymphoma and has substantial activity in this setting both alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are seeking to optimize the dose and schedule of rituximab through ‘maintenance’ strategies exploring chemotherapyrituximab combinations and the use of other biologic agents or antibodies that may enhance activity when employed together with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease and have potential utility as part of initial treatment as well. In diffuse large B-cell lymphoma, the addition of rituximab to CHOP chemotherapy can improve survival, though benefits are more limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled immunotherapies are ongoing in order to optimize their use for maximal clinical benefit.     

Observation of the Curative Effect of Mabthera in Combination with the CHOP Regimen in Treating Invasive B-Cell Lymphoma： A Report of 45 Cases

OBJECTIVE To observe the clinical effcacy and toxic effects of Mabthera (rituximab) in combination with the CHOP (R-CHOP) regimen for treating invasive B-cell non-Hodgkin’s lymphoma. METHODS A total of 45 patients with CD20 positive B-cell non-Hodgkin’s lymphoma were randomly divided into the R-CHOP (22 cases) and CHOP groups (23 cases for controls).They received the regimens of Mabthera in combination with CHOP or single CHOP therapy respectively.An appraisement of the curative effect could only be performed following 4 cycles of chemotherapy for the 45 patients.Follow-up was conducted to observe the conditions of survival. RESULTS The rate of complete remission(CR)in the R-CHOP group was 68.2%,with a total effective rate of 81.8%,and in the CHOP group these rates were 34.8% and 78.3% respectively.There was a significant difference in comparing the CR rates between the two groups (P<0.05).The 1,2 and 3-year overall survival (OS) rates of the RCHOP group were 90.9%,81.8% and 77.3%,respectively.In the CHOP group,the OS rates were respectively 91.3%,69.5% and 47.8%.The difference in the 3-year OS between the two groups was significant (P<0.05).The toxic effects of the two groups were mainly a slight and moderate bone marrow depression and a gastrointesinal reaction,with similar tolerable toxic effects in the two groups (P>0.05). Adverse effects related to the Mabthera infusions occurred in 6 cases of the R-CHOP group (27.2%).These effects lessened after symptomatic treatment. CONCLUSION The therapeutic regimen of Mabthera,in combination with CHOP (R-CHOP) has an obvious curative effect for treating invasive B-cell non-Hodgkin's lymphoma,with a favorable tolerance.It is highly recommended as the treatment of choice.     

Extranodal marginal zone B‐cell lymphoma of the lung: experience with fludarabine and mitoxantrone‐containing regimens

Bronchial‐associated lymphoid tissue (BALT) lymphoma is an extranodal primary pulmonary lymphoma. The optimal therapy for this rare disease is still debated, and few heterogeneous data are available in literature. The aim of our study was to critically review data of patients with BALT lymphoma treated in first‐line therapy with fludarabine and mitoxantrone‐containing regimens (with or without rituximab) to investigate the effectiveness and the safety of this approach and patients' survival. An observational retrospective study was performed on homogenous clinical data from 17 patients with biopsy‐proven diagnosis of BALT. All the patients were treated with fludarabine and mitoxantrone‐containing regimen therapy. Radiological findings were also reviewed to assess the role of ¹⁸fluoro‐deoxyglucose positron emission tomography in the initial assessment and in the monitoring of this extranodal lymphoma. A high percentage of response was observed: 82.3% of patients achieved a complete response, 11.8% a partial response. Furthermore, a very remarkable progression‐free survival (71%) and overall survival (100%) were estimated at 14 years. No relevant toxicities were registered. Our results support the use of fludarabine and mitoxantrone‐containing regimens as first‐line therapy in the treatment of BALT lymphoma even if further data are necessary to consolidate our findings. Positron emission tomography scanning may provide additional valuable information in the assessment of BALT lymphoma. Copyright © 2012 John Wiley & Sons, Ltd.     

Phase II study of oral fludarabine in combination with rituximab for relapsed indolent B-cell non-Hodgkin lymphoma

Oral fludarabine is more convenient than intravenous fludarabine in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine in combination with rituximab in patients with relapsed indolent B-cell non-Hodgkin lymphoma (B-NHL), we conducted a multicenter phase II study. Patients with relapsed indolent B-NHL with two or fewer prior regimens and up to 16 doses of rituximab were eligible. Patients received 375 mg/m² rituximab on day 1, and 40 mg/m² oral fludarabine once daily on days 1 through 5 every 28 days for up to six cycles. The primary endpoint was the overall response rate. Forty-one patients were enrolled, including 38 (93%) with follicular lymphoma. Thirty-four patients (83%) had received rituximab as prior therapy. Twenty-seven patients (66%) completed the planned six cycles. Dose reduction of oral fludarabine was required in 17 patients (41%). The overall response rate was 76% (31 of 41 patients; 95% confidence interval, 60–88%) with a complete response rate of 68% (28 of 41 patients; 95% confidence interval, 52–82%). Median progression-free survival for the 41 patients was 19.7 months (95% confidence interval, 12.3–26.5 months). Hematological toxicities, including grade 4 neutropenia (68%), were the most frequent toxicities. Non-hematological toxicities were mild, except for one patient who died of Pneumocystis jiroveci pneumonia 4 months after the protocol treatment. In conclusion, oral fludarabine in combination with rituximab is a highly effective and convenient therapy for patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab. (ClinicalTrials.gov number, NCT00311129.) ( Cancer Sci  2009; 100: 1951–1956)     

Loss of CD20 antigen expression after rituximab therapy of CD20 positive B cell lymphoma (diffuse large B cell extranodal marginal zone lymphoma combination): A case report and review of the literature

Rituximab (the chimeric anti-CD20 antibody) is widely used in the treatment of CD20 positive non-Hodgkin’s lymphoma (NHL). The response rate at relapse after repeated use in prior CD20 positive responders is lower than 50%. Several mechanisms can be responsible for rituximab resistance. CD20 negative relapses which transformed from CD20 positive aggressive and indolent forms of lymphoma can be the one of the reason of secondary resistance to rituximab. The authors report a case with combination of aggressive and indolent form of lymphoma who relapsed after 7 months from the last dose of rituximab therapy. CD20 transformed negative from positive in her relapsed disease. Patients with CD20 positive B cell NHL must rebiopsy after first line rituximab therapy if their disease relapsed or progressed.     

Phase II study of low-grade non-Hodgkin lymphomas with fludarabine and mitoxantrone followed by rituximab consolidation: Promising results in marginal zone lymphoma

The majority of patients with indolent lymphomas relapse due to minimal residual disease (MRD). In the present study, we sought to determine whether by using rituximab consolidation, for eradication of MRD, following induction chemotherapy with fludarabine and mitoxantrone (FN) combination could improve the outcome of indolent lymphomas. Patients with indolent lymphoma received fludarabine 25 mg/m² Day 1 - 3 and mitoxantrone 10 mg/m² on Day 1 every 28 days. Patients who attained a response (complete response, CR or partial response, PR) received four weekly doses of Rituximab 375 mg/m² 1 month and 3 months after completion of treatment. Forty-five patients were entered into this Phase II trial. The median follow-up time was 39 months. The median number of delivered cycles was 6. Fifty-three percent of patients attained a CR and 38% a PR for an overall response rate of 91%. One patient had stable disease, one had progression of the disease, whereas 2 were non-evaluable. After a median follow-up of 39 months, 32 of 46 patients (74%) are alive and disease-free. Grade III and IV toxicities included leucopenia (37%), neutropenia (28%), thrombocytopenia (7%), anemia (4%), and diarrhea (2%). Grade V toxicities included septic death in one patient and death due to hepatititis B reactivation 6 months after the last Rituximab dose in another patient. FN followed by R consolidation is a well-tolerated and active regimen in the treatment of patients with indolent lymphomas. Further follow-up is required to determine if these remissions are maintained.     

A new effective treatment for indolent lymphoma: a pilot study with fludarabine,idarubicin and prednisone combination (FLIDA)

The management of indolent lymphomas is still controversial. Intensive therapies may improve remission rate but in association with toxicity. Fludarabine and idarubicin are very active drugs in indolent lymphomas. This pilot trial was designed to evaluate the efficacy of a regimen comprising fludarabine, idarubicin and prednisone (FLIDA) in the treatment of low-grade non-Hodgkin's lymphoma at diagnosis. We have assessed the response of 16 adult patients (median age 57 years, range 45–71 years) treated on an outpatient basis: the overall response rate was 93.8 per cent (CR 43.8 per cent, PR ≥50 per cent). The toxicity of this regimen was very low, with no relevant hematological and infectious complications. © 1997 John Wiley & Sons, Ltd.