Caspase 3 Expression in Mantle Cell Lymphoma: An Immunohistochemical Study of 84 Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4676-4676
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Paul Riis ◽  
Peter Meusers ◽  
Guenter Brittinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Caspase 3 ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
Overall Survival Time ◽  
Mantle Cell ◽  
Median Overall Survival Time

Abstract Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. We investigated immunohistochemically the expression of the apoptotic marker caspase 3 in relation to the clinical course. Biopsy specimen from 84 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, Caspase3. The Caspase3 expression was analyzed in three groups: less than 1 positive cell per high power field (HPF), more than 1 positive cell per HPF and more than 2 positive cells per HPF. The expression was compared with the overall survival data analysed according to Kaplan and Meier. In 75 cases the caspase 3 staining could be analyzed. The caspase 3 expression had a range of 0.1–4.7 positive cells per HPF (median value:1.1, mean:1.3). Patients with mantle cell lymphoma that had less than 1 caspase 3 positive cell per HPF (33 cases) had a median overall survival time of 48 months compared to 27 months for patients with more than 1 positive cell per HPF (24 cases) and 15 months for more than 2 positive cells per HPF (18). The Kaplan-Meier analysis showed a significant difference in the overall survival time between these groups (p<0.0001). The immunohistochemical detection of caspase 3 in mantle cell lymphoma is a predictor for survival in MCL.

Apoptosis Regulating Proteins bax and p53 in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4710-4710
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Dirk Janssen ◽  
Paul Riis ◽  
Peter Meusers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
P53 Expression ◽  
Overall Survival Time ◽  
Mantle Cell ◽  
Median Overall Survival Time

Abstract In malignant tumors beside cell proliferation also cell death plays role for cell survival. Apoptosis regulating genes can be divided into two groups: death antagonists and death agonists such as bax. The ratio of death agonists and antagonists determines if a cell goes into apoptosis. We investigated in a large collective the immunohistochemical expression of the apoptotic marker p53 and bax in relation to the clinical course. Biopsies were stained immunohistochemically with monoclonal antibodies against bax and p53 and the expression was subdivided in three groups: negative, weak positive and strong positive. The expression profiles were analyzed with the overall survival data according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative p53 expression had a median overall survival time of 38.1 months compared to 22.3 months for patients with a weak and 11.3 months for a strong p53 expression (0<0.0001). The bax expression was in the majority of cases positive. Only one case showed a negative staining. Patients with weak and strong bax expression showed no differences in clinical outcome (median overall survival time: 23 vs 33 months, p=0.6051). The immunohistochemical detection of p53 in mantle cell lymphoma is a good predictor for the clinical outcome.

Immunohistochemical Detection of CD95L (Fas Ligand) in Mantle Cell Lymphoma: A Prognostic Factor for Clinical Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4566-4566
Author(s):  
Carsten Schrader ◽  
Peter Meusers ◽  
Guenter Brittinger ◽  
Dirk Janssen ◽  
Reza Parwaresch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Fas Ligand ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
Immunohistochemical Detection ◽  
Overall Survival Time ◽  
Mantle Cell

Abstract Mantle cell lymphoma is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. Proliferation indices are important prognostic factors in the clinical outcome. We investigated immunohistochemically the expression of the apoptotic marker CD95L (Fas Ligand) in relation to the clinical course. Biopsy specimen from 69 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, CD95L. The CD95L expression was analyzed into three groups: negative, weak positive and strong positive. The expression was compared with the overall survival data analysed according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative and weak positive CD95L expression had a median overall survival time of 32.0 months compared to 18.3 months for patients with a strong CD95L expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time between the patients with strong CD95L expression and the group of patients with negative or weak positive tumor cells (p&lt;0.0038). Based on these findings, the immunohistochemical detection of CD95L in mantle cell lymphoma is a prognostic factor.

Mantle-cell lymphoma: a population-based clinical study.

1996 ◽  
Vol 14 (4) ◽  
pp. 1269-1274 ◽  
Author(s):  
G A Velders ◽  
J C Kluin-Nelemans ◽  
C J De Boer ◽  
J Hermans ◽  
E M Noordijk ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Cell Lymphoma ◽  
Population Based ◽  
Response To Therapy ◽  
Comprehensive Cancer Center ◽  
Overall Survival Time ◽  
Mantle Cell

PURPOSE From a population-based non-Hodgkin's lymphoma (NHL) registry, 41 patients with mantle cell lymphoma (MCL) -- a recently defined distinct B-cell NHL -- were selected and compared with patients with low- or intermediate-grade NHL from the same registry. PATIENTS AND METHODS The incidence and behavior of MCL in the area of the Comprehensive Cancer Center West (CCCW) from 1981 to 1989 were analyzed. Age, performance, tumor bulk, extranodal localization, stage, response to therapy, and survival were registered. Expression of cyclin D1 protein and Ki-67 were measured in 29 patients. RESULTS MCL made up 3.7% of NHLs. The median age was 68 years, and the male-to-female ratio was 1.6:1. Seventy-eight percent presented with stage IV, with the majority having bone marrow involvement. The complete response (CR) rate was 32% (13 of 41), with a median duration of 25 months. The median overall survival time was 31.5 months. The International Prognostic Index identified five patients with a low-risk score and a median survival time of 93+ months. In 23 of 29 patients, cyclin D1 overexpression was present, without any relation to overall or disease-free survival. In contrast, a proliferative index less than 10% was significantly related to a better overall survival time (50 v 24 months). CONCLUSION MCL is a disease of the elderly, who present with widespread disease and with a poor response to therapy. Although it harbors features of an indolent NHL, it behaves clinically as an aggressive NHL with a short overall survival time.

SOX11 Expression Versus Indolent Clinical Course in Mantle Cell Lymphomas in a Population-Based Cohort From the Stockholm Region – SOX11 Negative Tumors Are Mostly p53 Positive, Contributing to Shorter Overall Survival,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3651-3651
Author(s):  
Birgitta Sander ◽  
Monika Klimkowska ◽  
Lina Nygren ◽  
Stefanie Baumgartner ◽  
Birger Christensson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cyclin D1 ◽  
Survival Time ◽  
Median Overall Survival ◽  
Clinical Course ◽  
Population Based ◽  
Mantle Cell ◽  
Sox11 Expression ◽  
Indolent Disease ◽  
Median Overall Survival Time

Abstract Abstract 3651 Introduction: Mantle cell lymphoma (MCL) constitutes 3–10% of non-Hodgkin lymphomas and has a median survival of 3–5 years. A small number of patients are characterized by a clinically indolent disease and may not require treatment for several years. However, these are difficult to identify at the time of diagnosis due to lack of reliable predictive markers. Recently, the nuclear expression of the transcription factor SOX11 has been suggested to be of prognostic value in MCL. Materials and Methods: All 186 patients diagnosed with MCL in the Stockholm region between January 1998 and June 2010 were included. Diagnosis was according to the WHO criteria and all cases were cyclin D1 positive by IHC and/or for t(11;14) by FISH. Clinical data from patient files, diagnostic biopsies and flow cytometry data were reviewed. Patients not requiring treatment within the first two years after diagnosis were retrospectively defined as indolent disease. Patients were further categorized in nuclear SOX11 negative (n=13) and nuclear SOX11 positive (n=160) cases and in cases with indolent (n=17) versus non-indolent disease course (n=169). The following variables were evaluated at the time of diagnosis: age, sex, Ann Arbor stage, ECOG, B-symptoms, Hb, LDH, albumin, lymphocytosis, leukocytosis, splenomegaly, nodal and bone marrow involvement, MIPI, indolent disease, blastoid morphology, expression of CD23, light chain, Ki 67, SOX11 and p53. Overall survival was analyzed, excluding patients receiving ASCT (n=37). Baumgartner, S. et al presents further data on the entire cohort in the accompanying abstract. Results: The following variables were significantly more common in SOX11 negative cases (Table 1): Lymphocytosis (p=0,045), high LDH (p=0,029) and p53 positivity (p<0,000). MIPI high risk was more frequent among SOX11 negative patients but did not reach statistical difference. There were no statistically significant differences in the frequency of splenomegaly or indolent disease among SOX11 negative and positive cases. Median overall survival time was 36,7 months in the whole cohort; 16,5 months in patients with SOX11 negative tumors and 39,3 months in patients with SOX11 positive tumors (p=0,015), excluding 37 patients (1 SOX11 negative, 38 SOX11 positive) receiving ASCT as part of first-line therapy. Patients with an indolent clinical course had significantly less often B symptoms (p=0,002), nodal presentation (p=0,019) and elevated LDH (p=0,040) than patients with a non-indolent disease, while none of the other factors analyzed reached statistical significance. Median overall survival time of patients with indolent disease was not reached (median follow-up time 41,7 months). 15/17 of the MCL cases with indolent clinical course expressed SOX11. Conclusions: In a population-based cohort of 186 cyclin D1 positive MCL, 8% lacked expression of nuclear SOX11 at diagnosis. There was no enrichment of patients with an indolent disease among SOX11 negative MCL. Instead patients with SOX11 negative MCL had a higher frequency of lymphocytosis and elevated LDH at diagnosis and a shorter overall survival. MCL lacking nuclear SOX11 expression at diagnosis were more frequently p53 positive which may contribute to shorter survival in the SOX11 negative MCL subset. Disclosures: No relevant conflicts of interest to declare.

Analysis of Nuclear Factor Kappa B in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4712-4712
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Dirk Janssen ◽  
Paul Riis ◽  
Peter Meusers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Survival Data ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
High Power Field ◽  
Overall Survival Time ◽  
Significant Difference ◽  
Mantle Cell

Abstract Gene expression profiles revealed that proliferation associated genes are important prognostic factors in the clinical outcome in mantle cell lymphoma (MCL). Beside this well accepted markers also analysis of apoptotic proteins are now under investigation. We investigated immunohistochemically the expression of the apoptotic marker NF-kB in relation to the clinical course in 89 patients enrolled in two multicenter prospective trials. Biopsies were recut and stained with mandatory antibodies (CD20, CD5, CD3, CD23, cyclin D1) and NF-kB. The NF-kB expression was analyzed in three groups: negative, cytoplasmatic positive and nuclear positive (more than 1/HPF). The expression was compared with the overall survival data analyzed according to Kaplan and Meier. In 13 cases a negative NF-kB staining was detected. Fifty-seven cases were positive only in the cytoplasma and in 17 cases more than 1 cell per high power field showed nuclear activity. Patients with mantle cell lymphoma that had negative and cytoplasmatic positive expression had a median overall survival time of 35.7 months compared to 22.4 months for patients with a nuclear NF-kB expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time (p=0.0121). The immunohistochemical detection of NF-kB in mantle cell lymphoma is possible and a tool to identify patients with a poor prognosis.

Bcl2 Expression Predicts Better Overall Survival in 90 Patients with Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4677-4677
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Dirk Janssen ◽  
Paul Riis ◽  
Peter Meusers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Survival Data ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
Biopsy Specimens ◽  
Mantle Cell ◽  
Apoptotic Marker ◽  
Low Levels ◽  
Bcl2 Expression

Abstract The expression of bcl2 was typically observed in follicular lymphoma with a t(14;18) but also in CLL and mantle cell lymphoma (MCL). Up to now no study investigated the expression of bcl2 in correlation with the clinical outcome in a large collective of patients with MCL. We investigated immunohistochemically the expression of the apoptotic marker bcl2 in relation to the clinical course. 90 biopsy specimens were investigated immunohistochemically with antibodies against CD20, CD5, CD3, CD23, cyclin D1 and bcl2. The expression was analyzed in three groups: negative, 5–50% positive cells (weak positive) and more than 50% positive cells (strong positive). The expression profils were compared with the overall survival data analysed according to Kaplan and Meier. In none of thae cases a negative staining was found. 16 cases (18%) had a weak and 74 cases (82%) a strong bcl2 expression. Patients with mantle cell lymphoma that had a weak positive expression (n=16) had a median overall survival time of 21 months compared to 32 months for patients with a strong expression (n=74) (p=0.0402). In contrast to DLBL high levels of bcl2 expression had a better prognosis than pathients with low levels.

Intensive Treatment Strategies May Not Provide Superior Outcomes in Mantle Cell Lymphoma: Overall Survival Exceeding Seven Years in a Large Cohort of Patients Managed Primarily with Conservative Therapies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1362-1362 ◽  
Author(s):  
Peter Martin ◽  
Amy Chadburn ◽  
Paul Christos ◽  
Richard R. Furman ◽  
Jia Ruan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Median Overall Survival ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Mantle Cell ◽  
First Remission

Abstract Historically, reported outcomes in patients with mantle cell lymphoma (MCL) have been poor, with a median overall survival cited in the range of 2 to 4 years. As a consequence, recent approaches to first-line treatment have become more aggressive. Single- and oligo-center non-randomized studies with R-Hyper-CVAD and/or autologous stem cell transplant in first remission have produced 3-year overall survival >80%, prompting many to consider them as optimal standard of care. However, a substantial fraction of MCL patients are ineligible to receive these regimens due to age and comorbidities. To determine whether these interesting results might be affected by patient referral/selection biases rather than a true superiority of therapy, we evaluated outcomes from our MCL patient cohort, a group potentially shaped by similar biases but largely managed in a more conservative fashion. As progression-free survival is likely improved by aggressive treatments, our focus is on overall survival given the central importance of this endpoint. Methods: We used pathology records to identify all patients with a diagnosis of MCL evaluated at the Weill Cornell Medical Center since 1997. Patients were considered eligible for inclusion if a date of diagnosis could be identified. In the subset where clinical records were limited, an online social security database was used to verify survival. Median overall survival was calculated according to the Kaplan-Meier method. Results: We identified 181 patients with the diagnosis of MCL established by standard hematopathologic criteria. Forty-eight of these cases were outside consults to our pathology department without available clinical data. Of the remaining 133 patients, date of diagnosis was identified in 111 subjects. Median age at diagnosis was 64 years (range: 37–88). For the subset of patients with available prognostic information, 81% were stage IV, 75% had bone marrow involvement, 52% had an IPI of ≥3. The median overall survival (N=111) was 7.1 years (85 months with 95% C.I. 63 to 98 mo.). Three-year overall survival was 86% (95% C.I. 78% to 92%). Adequate information on therapy was available for 75 patients. Most patients were treated with CHOP-like regimens. Only 5 were treated with (R)-Hyper-CVAD or autologous stem cell transplant in first remission while an additional 4 patients received one of these regimens as subsequent therapy, Five patients survived longer than 10 years—one patient is alive at 15.4 years—despite never receiving Hyper-CVAD or autoSCT. Univariate analysis of treatment type revealed no significant effect on overall survival. Conclusions: Our data demonstrate that single-center outcomes with conservative approaches in MCL can yield similar overall survival to that achieved with more intensive approaches at other single-centers. Therefore patient referral/selection biases may substantially account for the perceived superiority of aggressive strategies. Intensive treatment approaches for MCL should not be considered superior with respect to overall survival in the absence of long-term data from multicenter randomized trials comparing them to more conservative strategies.

Subcutaneous Alemtuzumab (MabCampath) in Fludarabine-Refractory CLL (CLL2H Trial of the GCLLSG).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3120-3120 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Dirk Winkler ◽  
Andreas Bühler ◽  
Thorsten Zenz ◽  
Silja Groner ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Survival Time ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Outpatient Basis ◽  
Free Survival ◽  
Overall Survival Time ◽  
Median Overall Survival Time ◽  
Grade Iii

Abstract Fludarabine-refractory CLL has a poor prognosis with a median overall survival time of less than 12 months despite salvage chemotherapy and intravenous alemtuzumab (Campath-1H) is the approved treatment based on a remission rate of 33% and a median survival time of 16 months (Keating et al., Blood 2002). The CLL2H trial of the GCLLSG was initiated to evaluate the subcutaneous application of 3 × 30 mg alemtuzumab weekly in fludarabine refractory CLL. The current analysis is based on 109 consecutive patients enrolled until completion of the trial in April 2006. Median age was 63 (36–81) years, 71% were male. A median number of 3 (1–9) prior lines of therapy had been given. Subcutaneous treatment was performed on an outpatient basis in all cases and had to be temporarily interrupted in 68 patients due to neutropenia (43%), anemia (6%), thrombocytopenia (3%), infections (40%, CMV reactivations 30%), and was stopped early in 63 cases due to insufficient response (44%), hematotoxicity (16%), infection (17%), and CMV reactivation (13%). The median alemtuzumab dose given was 722 (3–2203) mg. Toxicity was mostly grade I/II apart from hematotoxicity (grade III/IV anemia: 42%, thrombocytopenia: 52%, neutropenia: 54%) and grade III/IV infections (25%). After a median follow up time of 21.4 months, 56 deaths have occurred (due to progression 52%, infections 39%, not CLL related 9%). The overall response rate was 33% (CR 4%, PR 27%), the median progression free survival time was 7.7 months, and median overall survival time was 19.1 months. Genetic high-risk factors were present in the vast majority of cases (unmutated VH 66%, 17p–29%, 11q–19%, TP53 mutation 39%). Responses (CR or PR) were observed in 22% of VH unmutated, 24% of 11q-, 39% of 17p-, and 33% of TP53 mutated cases. Progression free survival and overall survival were not significantly different when comparing the genetic subgroups, particularly TP53 mutated, 11q-, and 17p- (see figure). In conclusion, subcutaneous alemtuzumab is feasible in an outpatient setting in a high-risk population of fludarabine-refractory CLL and appears to be of similar efficacy as by intravenous administration. Most importantly, genetic high risk subgroups with unmutated VH, 11q- or 17p- appear to respond to alemtuzumab. Figure Figure

scholarly journals Contribution of intraoperative stimulation mapping to glioblastoma surgery within or adjacent to descending motor pathways: survival analysis and functional outcome comparison between two series in a single institution

2021 ◽  
Author(s):  
Jimmy Ming-Jung Chuang ◽  
Li-Han Lin ◽  
Meng-Hsiang Chen ◽  
Wei-Che Lin ◽  
Cheng-Hsien Lu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Time ◽  
Neurological Outcome ◽  
Median Overall Survival ◽  
Extent Of Resection ◽  
Rank Test ◽  
Positive Effects ◽  
Overall Survival Time ◽  
Significant Difference ◽  
Median Overall Survival Time

Abstract Purpose Extensive resection probably confers a modest survival advantage in patients with glioblastoma. Studies have revealed the positive effects of intraoperative stimulation mapping (ISM) on the extent of resection, but no consensus for contribution of intraoperative stimulation mapping is reached. Methods This retrospective study enrolled two groups of patients who underwent surgery for motor-eloquent glioblastoma: the non-ISM group of 57 patients (surgery in 2008–2013) and ISM group of 13 patients (surgery in 2014–2015). The two groups and subgroups based on resection extent and postoperative additional neurological deficit were compared using Kaplan–Meier analysis and the log-rank test. Results Gross or near total resection (≥ 90% resection quality) was significantly more common in the ISM group than the non-ISM group (76.9% versus 24.6%; p = 0.001). The extent of resection was also significantly greater (90.5% ± 15.6% versus 64.6% ± 29.2%; p = 0.002). The neurological outcome in the ISM group was thus superior, but the two differences were not significant. The median progression-free survival time was significantly longer in the ISM group (22.0 ± 5.1 months vs 8.0 ± 1.0 months; p = 0.037) but a significant difference was not indicated in median overall survival time (22.0 ± 8.4 months vs 16.0 ± 2.2 months; p = 0.167). Conclusion ISM was discovered to lead to higher quality of resection and delayed recurrence. The neurological outcome and median overall survival time in the ISM group was thus superior, but the two differences were not significant. Trial registration number (for clinical trials) Nil

Modified Topotecan Combination with Cyclophosphamide and Ara-C (CAT) for Patients with Refractory/Relapsed Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4357-4357
Author(s):  
Sui-jing Wu ◽  
Xin Du ◽  
Wei Lin ◽  
Zi-lun Huang ◽  
Xiao-li Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Survival Time ◽  
Median Time ◽  
Topoisomerase I ◽  
Median Overall Survival ◽  
Blast Phase ◽  
Platelet Recovery ◽  
Overall Survival Time ◽  
Median Overall Survival Time

Abstract The prognosis of patients with leukemia has improved significantly. With combination chemotherapy, 60%–80% of adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia(ALL) achieve complete remission(CR). But most patients eventually relapse and do not response to current induction regimens based on cytarabine and anthracyclines any more. This emphasize the need to discover new agents for the treatment of leukemia to improve long-term prognosis. Topotecan is a semisynthetic analogue of the alkaloid camptothecin which acts as a specific inhibitor of topoisomerase I,by stabilization of the topoisomerase I DNA complex which leads to cell death.It also appears to be active against leukemias which have acquired the multi-drug resistant phenotype.[ Ulukan et al. Drug, 2000; Weihrauch et al. Leuk Lymphoma, 2004].It also could go through blood brain barrier[Kollmannsberger et al. Oncology, 1999].Here we observe the effect and side-effects of cyclophosphamide, cytanthetic analogue of rabine and topotecan (Modified CAT) combination regimen for treatment of refractory or relapsed leukemia. The study population comprise 26 patients with relapsed/refractory leukemia,including 12 with AML, 9 with ALL, 2 with myeloid blast phase of CML, 3 with lymphoma. Median age was 35 years.Patients received cyclophosphamide 300mg/m2 every 12 hours for 6 doses on day1 to 3.On day 2, topotecan was given at a dose of 1.5mg/m2/day for 5 days on days 2 to 6, and cytarabine 1.0 g/m2 /day for 5 days on days 2 to 6.The regimen (cytarabine reduced to 0.5g/m2 /day) could be repeated one or two cycles after remission. The total response rate of one course was 57%, eleven patients (42%) achived complete remission(CR). Responses occurred in 7of 12 AML (57%), including 5 CR(41%); in 6 of 9 patients with ALL (67%), including 5 CR(56%); and in 1 of 2 myeloid blast phase of CML(CR 50%). The median overall survival time after treatment was 2+ months, and the median overall survival time after CR was 4+ months. Severe myelosuppression was universal (100% Grade 4 neutropenia and thrombocytopenia), the median time to recovery of neutrophils to ≥0.5×109/L was 18 days,and the median time to platelet recovery to ≥ 20×109/L was 26 days.Infection developed in 96% cases, the most frequent events were oral mucositis(77%, 20/26), sepedogenesis(46%, 12/26),anusitis(38%,10/26),pneumonia(31%, 8/26), two patients died of infection complications(8%). Non-hematologic toxicity was seen frequently in gastrointestinal but it was mild. Nausea and/or vomiting occurred in 13 patients(50%)with gradeI-II in all of them.Two patients(8%) had diarrhea and grade 1–2 in them. In summary, Modified CAT regimen is well tolerated and has significant anti-leukemia activity as salvage therapy for relapsed/refractory leukemia.

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