The development of targeted chemotherapy for CNS lymphoma—a pilot study of the IDARAM regimen

Purpose We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination.Patients and methods In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM which comprised idarubicin 10 mg/m² i.v., days 1 and 2; dexamethasone 100 mg, 12-h infusion, days 1, 2 and 3; cytosine arabinoside (ARA-C) 1.0 g/m², 1-h infusion, days 1 and 2; methotrexate 2.0 g/m², 6-h infusion, day 3 (with folinic acid rescue); and cytosine arabinoside 70 mg plus methotrexate 12 mg, intrathecally, days 1 and 8. Two cycles were delivered at 3-weekly intervals. After response assessment, patients received adjuvant cranial radiotherapy (40 Gy over 20 fractions).Results The series comprised 24 patients, 11 male and 13 female. Their median age was 53 years (range 21 to 73 years). Grade 4 neutropenia and thrombocytopenia occurred in the majority of patients treated. Of the eight PCNSL patients, seven achieved complete remission (CR). Four remained in CR at the time of this report with a median duration of follow-up of 25 months (range 11 to 42 months). Of the 16 SCNSL patients, 12 achieved CR. Seven patients remained in CR at the time of this report with a median duration of follow-up of 24 months (range 18 to 57 months).Conclusion This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL and is suitable for further development and evaluation.This work is presented on behalf of the Central and Southern Lymphoma Group.     

Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma

There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported. Here we retrospectively review the outcomes and toxicities of standard and modified doses of pemetrexed as salvage therapy in 18 PCNSL and 12 SCNSL patients. The overall response rate for PCNSL patients was 64.7 %, all of whom achieved a complete response (CR). The median progression-free survival (PFS) was 5.8 months. For the SCNSL patients, RR was 58.3 % with 2 CR (16.7 %); the median PFS was 2.5 months. Grade ≥3 adverse events included leukopenia in 5 patients (16.7 %), neutropenia in 1 patient (3.3 %), and fatigue in 3 patients (10.0 %). 3 patients died while on treatment, 2 due to infections and 1 due to pulmonary embolism. Our results indicate that pemetrexed has activity as salvage therapy in recurrent PCNSL, even with modified dosing, but outcomes trend towards less favorable in SCNSL.     

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa,Busulfan, and Cyclophosphamide Conditioning Regimen

BackgroundHigh-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.Patients and MethodsA retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).ResultsThe 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.ConclusionHDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.     

The value of bone marrow biopsy for staging of patients with primary CNS lymphoma

BackgroundIn patients with presumed primary CNS lymphoma (PCNSL), a systemic manifestation is found only in a small minority. Although bone marrow biopsy (BMB) is recommended for staging, its diagnostic value is unclear.MethodsA retrospective analysis of 392 patients with presumed PCNSL from 3 university hospitals and 33 patients with secondary CNS lymphoma (SCNSL) and initial CNS involvement from a multicenter Germany-wide prospective registry was performed.ResultsA BMB was performed and documented in 320/392 patients with presumed PCNSL; 23 had pathologic results. One harbored the same lymphoma in the brain and bone marrow (BM), 22 showed findings in BM discordant to the histology of brain lymphoma; n = 12 harbored a low-grade lymphoma in the BM, the other showed B-cell proliferation but no proof of lymphoma (n = 5), monoclonal B cells (n = 3), or abnormalities not B-cell-associated (n = 2). In the group of SCNSL with initial CNS manifestation, 32/33 patients underwent BMB; 7 were documented with bone marrow involvement (BMI); 1 had concordant results in the brain and BM with no other systemic manifestation. Six had additional systemic lymphoma manifestations apart from the brain and BM.ConclusionsIn only 2 out of 352 (0.6%) patients with CNS lymphoma (320 presumed PCNSL and 32 SCNSL), BMB had an impact on diagnosis and treatment. While collected in a selected cohort, these findings challenge the value of BMB as part of routine staging in presumed PCNSL.     

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.     

Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma.

PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.     

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma:a prospective phase Ⅱ trial

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone(R-FPD) regimen followed by whole-brain radiotherapy(WBRT) for patients with primary central nervous system lymphoma(PCNSL).Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen cons...     

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.     

Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas

IntroductionStandard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors.Patients and MethodsAll consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsAmong 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively].ConclusionIn patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.     

EPOCH方案治疗侵袭性非霍奇金淋巴瘤近期疗效观察

目的观察EPOCH方案治疗侵袭性非霍奇金淋巴瘤（NHL）的疗效和副作用。方法31例非霍奇金淋巴瘤患者采用EPOCH方案治疗。EPOCH方案：依托泊苷（VP-16）50mg／m2,表柔比星（E．ADM）12mg／m2,长春新碱（VCR）0．4mg／m2,溶解于生理盐水500ml中,持续静滴24h,第1～4天;环磷酰胺（CTX）750mg／m2静脉推注,第5天;强地松60mg／m2,口服,第1～5天,21天为1个周期,共进行4—6个周期。结果31例患者总有效率为90．3％,完全缓解（CR）率为64．5％,部分缓解（PR）率为25．8％,主要不良反应为骨髓抑制、脱发、黏膜炎。结论EPOCH方案是NHL经济、有效的治疗方案,毒性可耐受,值得在临床上推广应用。     

High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962.

PURPOSE: To confirm the feasibility and estimate the efficacy of methotrexate (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy combined with radiotherapy (RT) for patients with non-AIDS-related primary CNS lymphoma (PCNSL) treated in a multicenter setting. PATIENTS AND METHODS: Treatment consisted of two cycles of MBVP (MTX 3 g/m2 days 1 and 15, teniposide 100 mg/m2 days 2 and 3, carmustine 100 mg/m2 day 4, methylprednisolone 60 mg/m2 days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response and safety of this regimen. RESULTS: Twelve centers included 52 patients who were all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27 months. One patient progressed and died before treatment, and five patients died during treatment. Four patients received RT after one cycle of chemotherapy, and 42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity was seen in 78% of patients for leukocytes and 24% of patients for platelets. The overall response rate of all 52 patients was 81%. Two patients who did not fulfill the criteria of objective response survived more than 1 year; one of them is still alive without disease. Eighteen patients died; 11 deaths were a result of tumor, five were probably treatment-related, one was caused by late leukoencephalopathy, and one was a result of intercurrent disease. Median estimated overall survival was 46 months. CONCLUSION: MBVP followed by RT for PCNSL has a high response rate. However, the 10% toxic death rate during treatment in a multicenter setting underlines the need for highly specialized care.     

ESHAP as salvage therapy for refractory non-Hodgkin's lymphoma: Taiwan experience

BACKGROUND: The ESHAP regimen, a combination of the chemotherapeutic drugs etoposide, methylprednisolone (solumedrol), high-dose cytarabine (ara-C) and cisplatin, has been shown to be active against refractory non-Hodgkin's lymphoma in therapeutic trials. We were interested in determining whether this regimen would be effective and tolerable for Chinese patients. METHODS: Thirty-two patients with refractory/relapsed non-Hodgkins lymphoma (23 intermediate-grade and nine high-grade) were enrolled in this study. Etoposide was administered at a dose of 40 mg/m2/day as a 1 h intravenous infusion from day 1 to day 4, solumedrol 500 mg/day was given as a 15 min intravenous infusion from day 1 to day 5, ara-C 2 g/m2 was given as a 2 h intravenous infusion on day 5 and cisplatin was given at a dose of 25 mg/m2/day as a continuous infusion from day 1 to day 4. Clinical efficacy and toxicity were assessed on the basis of the WHO criteria. RESULTS: Ten patients (31.3%, 95% Cl 15.2-47.4%) attained complete remission (CR) and seven had partial remission (PR). The overall response rate was 53.1% (95% Cl 35.8-70.4%). In eight of the 10 CR patients, the remission lasted for more than 8 months. The remaining two patients had CR of 5 and 6 months. The median duration of CR was 12.2 months (range 5-22 months). Myelosuppression with subsequent infections was the major toxicity. Severe leukopenia (WBC < 1000/microliter) lasted for an average of 12 days and thrombocytopenia (< 25,000/microliter) 18 days. One patient (3.1%) died of neutropenia-associated sepsis within 4 weeks after treatment. Non-myeloid toxicities included alopecia in 66% (28% grade 2, 22% grade 3), stomatitis in 72% (25% grade 2, 28% grade 3, 13% grade 4), hepatotoxicity in 9% (3% grade 2), renal toxicity in 13% (6% grade 2, 3% grade 3) and infection in 56% (18% grade 2, 25% grade 3, 13% grade 4). The majority of the responders relapsed within 2 years after ESHAP treatment. Median survival for all patients was 8.6 months. CONCLUSIONS: ESHAP is an active and tolerable regimen in Chinese patients with relapsed/refractory lymphoma, but the duration of remission is brief and without significant impact on survival.     

BACOD方案治疗复发及难治性非霍奇金淋巴瘤的临床研究

 目的　观察BACOD方案治疗复发及难治性非霍奇金淋巴瘤（NHL）的疗效及患者不良反应。方法　65例复发及难治性NHL患者,采用BACOD方案进行化疗,具体为：博莱霉素10 mg／m2,静脉滴注,第2、9天;环磷酰胺750 mg／m2,静脉滴注,第1天;长春地辛3 mg／m2,静脉注射,第1、8天;阿糖胞苷150 mg／m2,静脉滴注,第2天至第5天;地塞米松10 mg／m2,静脉滴注,第1天至第7天,3周为1个疗程。结果　完全缓解18例,部分缓解30例,稳定13例,进展4例,有效率70.8 %。有效患者中位缓解时间 10个月（2～35个月）。1年生存率32.3 %,2年生存率24.6 %。患者主要不良反应为骨髓抑制。结论　BACOD方案可作为复发及难治性NHL的解救方案。     

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.     

恩度联合多西紫杉醇和顺铂一线治疗晚期食管鳞癌的疗效

 目的 观察恩度（YH-16）联合多西紫杉醇（DOC）和顺铂（DDP）一线治疗晚期食管鳞癌的疗效及不良反应。方法 27例经组织学证实的晚期食管鳞状细胞癌患者,其中16例接受DOC／DDP方案化疗,11例接受YH-16／DOC／DDP方案化疗。DOC／DDP组：DOC 60mg／m2 d1 1小时内静脉输注,DDP 30mg／m2 d1~3 2小时静脉输注,21天为一周期;YH-16／DOC／DDP组：DOC/DDP用法同上,YH 16 7.5 mg／m2 d1~14 3～4小时静脉输注,21天为一周期。每化疗2周期后按RECIST标准评价疗效,每1周期后根据CTCAE3.0进行不良反应分级。结果 DOC／DDP组,PR 6例（37.5%）,总有效率37.5%（CR+PR）;中位至疾病进展时间（TTP）142天,中位生存时间（OS）310.5天。YH 16／DOC／DDP组CR 1例（9%）,PR 4例（36.4%）,总有效率45.4%（CR+PR）;中位至疾病进展时间（TTP）210天,中位生存时间（OS）371天。两组比较TTP及OS差异均无统计学意义。DOC／DDP组和YH 16／DOC／DDP组3～4级血液系统不良反应包括：白细胞减少（44% vs. 45%）,中性粒细胞减少（38% vs. 27%）,中性粒细胞减少性发热（6% vs. 9%）;非血液系统不良反应主要为1～2级的恶心呕吐,其发生率分别为50%和45%。无治疗相关性死亡。结论 恩度联合多西紫杉醇和顺铂一线治疗晚期食管鳞癌不延长TTP及OS。     

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.     

Prospective trial on topotecan salvage therapy in primary CNS lymphoma.

BACKGROUND: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL. PATIENTS AND METHODS: The study included 27 patients with a median age of 51 years and an ECOG performance status of 2. Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months. Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m(2) for 5 days was repeated every 3 weeks. RESULTS: The response rate was 33% with five complete (CR) and four partial remissions (PR). The median follow-up was 37.7 months. All complete responders had sustained remissions lasting for 9 to 28 months. The median event-free survival (EFS) was 2.0 months (9.1 months in responders), the overall survival (OAS) was 8.4 months. CTC grade 3-4 leukopenia occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients alive without cerebral lymphoma > or = six months after topotecan exhibited deficits attributable to late neurotoxicity. CONCLUSION: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.     

BTK抑制剂在中枢神经系统淋巴瘤中的治疗作用及安全性分析

目的：研究布鲁顿酪氨酸激酶（Bruton’s tyrosine kinase,BTK）抑制剂治疗复发/难治性中枢神经系统淋巴瘤(relapsed/refractory central nervous system lymphoma,R/R CNSL）的有效性和安全性。方法：回顾性分析郑州大学第一附属医院2018年10月至2021年10月收治的43例R/R CNSL患者,分别使用BTK抑制剂单药、BTK抑制剂联合化疗、BTK抑制剂联合免疫治疗方案,BTK抑制剂包括伊布替尼、泽布替尼、奥布替尼,初始剂量分别为（420～560）mg/d、320 mg/d、（100～150）mg/d,分析治疗后的最好疗效和不良反应。结果：BTK抑制剂单药组（A组）、BTK抑制剂联合化疗组（B组）、BTK抑制剂联合免疫治疗组（C组）的客观缓解率（objective response rate,ORR）分别为44.4%、85.7%和76.9%,B组的ORR高于A、C组,原发中枢神经系统淋巴瘤（primary CNSL,PCNSL）患者的ORR(78.6%vs. 66.7%)高于继发中枢神经系统淋巴瘤（second...     

以替尼泊甙为主的化疗方案相伴放疗治疗小细胞肺癌

目的探讨替尼泊甙（ＶＭ－２６）为主的化疗方案相伴放疗治疗小细胞肺癌的临床疗效。方法５３例小细胞肺癌中，４８例选用ＶＭ－２６＋顺铂（ＤＤＰ）方案，ＶＭ－２６每天６０ｍｇ／ｍ２，ＤＤＰ每天２５ｍｇ／ｍ２，连用３天为一个疗程；另５例用卡铂取代ＤＤＰ，５００ｍｇ静脉滴注，１天完成。除第１个与第２个疗程化疗间隔４０天左右外，以后每４周重复１个疗程，共５个疗程。在第１个疗程化疗后１～４天内开始放射治疗。对局限期和广泛期患者分别照射不同的剂量和部位。结果局限期患者近期疗效为９７．８％［完全缓解（ＣＲ）为５３．３％，部分缓解（ＰＲ）为４４．８％］，１年和２年生存率分别为７７．１％（２７／３５）和４４％（１１／２５），中位生存期大于１８个月。广泛期患者近期疗效为７５％（ＣＲ２５％），一年生存率为３７．５％（３／８），中位生存期大于１１个月。结论以ＶＭ－２６为主的化疗方案相伴放疗是治疗小细胞肺癌的有效方案，可提高肿瘤的局部控制率。