Diagnostic and prognostic significance of CD200 expression and its stability in plasma cell myeloma

2014 ◽  
Vol 67 (9) ◽  
pp. 792-796 ◽  
Author(s):  
Jonathan J Douds ◽  
Daniel J Long ◽  
Annette S Kim ◽  
Shaoying Li
Keyword(s):  
Plasma Cell ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Plasma Cell Myeloma ◽  
Membrane Expression ◽  
Bone Marrow Biopsies ◽  
Prognostic Effect ◽  
Significant Difference ◽  
The Stability

AimPrevious studies showed that CD200 expression is a prognostic factor for plasma cell myeloma (PCM), but the prognostic effect is conflicting between studies. We studied CD200 protein expression and the stability of expression in PCM to clarify its potential utility in diagnosis, prognosis and monitoring of disease.MethodCD200 expression was studied in 77 cases of PCM by immunohistochemistry on paraffin sections from decalcified bone marrow biopsies.ResultThere were 16 newly diagnosed cases and 61 post-treatment cases from 54 patients: 37 men and 17 women, with a median age of 62 years (range, 41–88 years). CD200 demonstrated moderate to strong membrane expression in positive cases. Fifty-six of 77 cases (73%) showed CD200 expression. Twenty of the 22 (91%) patients with serial specimens demonstrated stable CD200 expression (n=15) or lack of CD200 expression (n=5). One patient lost CD200 expression, while another one gained CD200 expression during treatment. The clinical, pathologic and cytogenetic features between the CD200+ group and the CD200− group were similar in most instances. However, CD200 expression was associated with lower serum β2-microglobulin (p=0.03). There was no significant difference in overall survival and progression-free survival between the CD200+ and CD200− patients (p>0.05).ConclusionsCD200 is expressed in a majority of PCM cases, and the expression is stable during the treatment process. Therefore, immunohistochemical expression of CD200 is a useful marker for the diagnosis and follow-up of PCM.

scholarly journals Prognostic Impact of Bone Marrow Erythropoiesis on Newly Diagnosed Plasma Cell Myeloma: A Single Institutional Analyses

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5579-5579
Author(s):  
Daniel E Ezekwudo ◽  
Rohit Singh ◽  
Bolanle Gbadamosi ◽  
Mark Micale ◽  
Ishmael Jaiyesimi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcome ◽  
Plasma Cell ◽  
Prognostic Impact ◽  
Plasma Cell Myeloma ◽  
Newly Diagnosed ◽  
Bone Marrow Biopsies ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Impact

Abstract Introduction: In plasma cell myeloma (PCM), tumor burden and activity plays an important role in diagnosis and prognosis (e.g. circulating plasma cells), however very little attention has been directed to the impact of the non-plasma cell component of the bone marrow. The presence of anemia has been used to distinguish PCM from smoldering myeloma; however this can be a non-specific finding as there are many potential causes of anemia besides PCM. We sought to determine if the level of erythropoiesis in bone marrow biopsies may be a more reliable prognostic factor. In the study herein, we assessed the level of bone marrow erythropoiesis in patients with newly diagnosed PCM, and compared those findings with cytogenetic results (CGs), other prognostic factors and overall clinical outcome. We hypothesized that patients with adequate erythropoiesis (AEp) are likely to have favorable cytogenetics and better outcome compared to those with decreased erythropoiesis (DEp). Methods: We retrospectively reviewed pathology database for bone marrow biopsies in patients with diagnosis of plasma cell myeloma (PCM) at Beaumont Hospital, an academic community center from 2012 and 2014. Biopsy cases without anemia were excluded. A total of 91 patients with plasma cell myeloma and anemia were identified. Each biopsy was re-examined to determine the level of erythropoiesis. The level of erythropoiesis was calculated by multiplying erythroid fraction (obtained from M:E ratio) with non-plasma cell bone marrow cellularity. Cases were separated into AEp and DEp using an erythroid compartment cut-off of 7.5% based on already established data. Kaplan-Meier analysis was used to compare survival between groups. Results: Demographic distribution of studied patients were 46 (50.1%) white, 39 (43%) African Americans and 6 (6.6%) others. Out of 91 cases analyzed, 38 (42%) had AEp whereas 53 (58%) had DEp. Among those with AEp, 23 (62%) had favorable CGs (defined as those without t (4, 14), t (14, 16), t (14, 20) or 17 p deletion); 15 (38%) had unfavorable CGs. Among those with DEp, 14 (26%) had favorable CGs whereas 39 (74%) had unfavorable cytogenetics. The vast majority of patients with favorable CGs were alive whether they had AEp (87%) or DEp (79%), thus CGs remained significant even after controlling for erythroid compartment (p = 0.03). Overall, those with AEp were noted to have significantly lower β-2 microglobulin (AEp median =2.42 mg/dL, DEp median = 4.50 mg/dL, p = 0.02). Kaplan-Meier analysis showed a significant difference in survival curves among the four groups (AEp with favorable CGs, AEp with unfavorable CGs, DEp with favorable CGs, DEp with unfavorable CGs, p<.0001). While the two groups with favorable CGs showed no significant difference (p=.6050), the two groups with unfavorable CGs did (p=.0027). Conclusion: Our findings suggest that patients with PCM and anemia are not a homogenous population. Assessment of the erythroid compartment in these patients reveals a population with AEp that has more favorable CGs and lower β-2 microglobulin than patients with DEp. Despite this finding, patients with favorable CGs had a favorable clinical outcome whether they had AEp or not, indicating that current therapies can overcome differences in erythropoiesis in that group. For patients with unfavorable CGs, however, those with AEp had superior survival outcome compared to those with DEp, indicating that there may be some prognostic or diagnostic utility to assessing erythropoiesis in patients who meet current criteria for PCM, and possibly, incorporating erythropoietic activity into diagnostic/prognostic schema. Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of the Plasma Cell Labeling Index (LI) in Newly Diagnosed Myeloma Patients Treated with Thalidomide-Dexamethasone (Thal/Dex) or Lenalidomide-Dexamethasone (Len/Dex).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1729-1729 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Philip R Greipp ◽  
Kristina M. Laumann ◽  
Sumithra Mandrekar ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Labeling Index ◽  
Cell Labeling ◽  
Separate Analysis ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Prognostic Effect ◽  
Significant Difference ◽  
The Impact

Abstract Background: The plasma cell labeling index (LI), a slide-based measure of the percentage of bone marrow plasma cells in the S-phase of cell cycle, is a powerful prognostic tool in multiple myeloma (MM). A high LI is a marker of poor outcome, and is a useful adjunct to cytogenetics and fluorescent in-situ hybridization to risk-stratify MM patients. It has been shown to provide additional prognostic information in International Staging System (ISS) stages 1 and 2 patients treated with conventional chemotherapy ± autologous stem cell transplantation. However, the impact of a high LI is not known in patients receiving novel agents that have been integrated into the current treatment paradigm of newly diagnosed MM. The objective of this study was to determine the value of LI in patients treated with thalidomide-dexamethasone (Thal/Dex) or lenalidomide-dexamethasone (Len/Dex). Patients and Methods : Data from 125 newly diagnosed MM patients enrolled in clinical trials with either thalidomide (200mg/d) plus dexamethasone (Thal-Dex; n=50), or lenalidomide (25 mg/d on days 1–21 of a 4-week cycle) plus dexamethasone (Len-Dex; n=75) as initial therapy, were utilized. Patients within both the studies were categorized into 2 LI groups based on baseline LI: high (≥1%) vs. low (&lt;1%) LI. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan Meier method, and compared between the two LI groups within the Thal Dex and Len-Dex studies using log rank tests. Results : The median follow-up for patients on Thal-Dex and Len-Dex was 7.5 and 3 years, respectively. 36% (18/50) of patients in the Thal-Dex study and 35% (26/75) in the Len-Dex study had high LI. The baseline patient-characteristics, including age, stage (ISS), lactate dehydrogenase, calcium, hemoglobin and creatinine were comparable between the 2 studies. The median OS for patients receiving Thal-Dex was 4.7 years (95% CI 3.1–8.1); 2.3 years (95% CI 1.3–4.6) for patients with LI ≥1 compared to 6.9 years (95% CI: 3.9–NA) for those with LI &lt;1 (P=0.02). The median OS for patients on Len-Dex was not reached for either the high or low LI group (P=0.80). The median PFS for all Thal-Dex patients was 1.7 years (95% CI: 1.4–3.1); 1.3 years (95% CI: 0.2–2.0) for patients with high LI vs.2.3 years (95% CI: 1.3–3.3) for patients with low LI; P = 0.01. The median PFS for Len-Dex patients was 2.6 years (95% CI: 1.8–3.1) years, and no significant difference was observed between the 2 LI groups, with PFS of 2.3 years (95% CI: 1.4–3.1) for patients with high LI, and 3.1 years for patients in the low LI group. Due to a shorter median follow-up of Len-Dex patients, a separate analysis censoring all patients in both the studies at 3 years was performed with similar results. Conclusion : LI remains a significant determinant of PFS and OS in newly diagnosed MM patients treated with Thal-Dex, with high baseline LI predicting poorer outcome. In contrast, during first 3 years of follow-up, the unfavorable prognostic effect of LI is not apparent with Len-Dex therapy, and longer follow-up is needed to determine if Len-Dex therapy overcomes the poor prognostic effect of high LI. Figure Figure

Radiotherapy (RT) potentiation with weekly (q1w) or standard every 3 weeks (q3w) cisplatin chemotherapy (CT) for locally advanced head and neck squamous cell carcinoma (HNSCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6056-6056 ◽  
Author(s):  
Yann Molin ◽  
Emilie Lavergne ◽  
Pascal Pommier ◽  
Severine Racadot ◽  
Xavier Montbarbon ◽  
...  
Keyword(s):  
Cox Model ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Included Study ◽  
Alternative Methods ◽  
Rank Test ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Significant Difference

6056 Background: Q3w CT is standard RT potentiation for HNSCC but its toxicity requires to look for new treatment’s modalities. The aim was to explore if q1w CT could be a safe and effective alternative. Methods: Patients (pts) treated by chemoradiation (CT-RT) for a HNSCC were retrospectively included. Study population was first described. Then overall (OS) and progression-free survival since the RT onset were performed. Survival distributions were estimated by Kaplan-Meier method and compared between CT groups using the Log-Rank test. Prognostic effect of CT group was explored using Cox model. Results: 266 pts treated between January 2004 and December 2008 were included: 170 and 96 pts respectively received q1w and q3w CT. At diagnosis, 46% had oropharynx lesions, 20% larynx, 17% hypopharynx and 14% oral cavity. 70% pts experienced surgery, 39% CT induction and a median dose of radiation of 64 Gy without any significant difference between CT groups. However, median age at diagnosis was significantly different between q1w and q3w CT (58 vs 54, p<0.001) as well as alcohol consumption (79% vs 68, p=0.047), stage at diagnosis (30%-60% stage III-IV vs 13% -80%, p=0.003), IMRT use (4% vs 13%, p=0.011) and median weight before RT (66 kg vs71kg, p=0.014). Q3w CT was more toxic than q1w in terms of weight loss (87% vs 75%, p=0.012), renal failure (50% vs 35%, p=0.022), worse CT plan completion (42% vs 66%, p<0.001). Moreover, grade 3/4 toxicities, such as mucositis (34% vs 13%, p<0.001) and dermatitis (7% vs 1%, p=0.012), were more frequent. More pts needed parenteral nutrition (10% vs 2%, p=0.008), analgesics (91% vs 70%, p<0.001), secondary hospitalization (31% vs 8%, p<0.001), RT interruption >= 3 days (8% vs 2%, p=0.037) and had long-term toxicities (24% vs 12%, p=0.014). With a median follow-up of 42 months 95% CI [36.8-48.8], a trend in favour of q3w CT was found:2-years OS of 83% (95% CI [73-90]) vs 74% (95% CI [66-80]), p=0.089. However, after adjustment on prognostic factors CT group was not significantly associated with OS nor with PFS. Conclusions: Q1w RT-CT is safer than q3w and may be as efficient. Follow-up data will be updated to reinforce efficacy results.

scholarly journals Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunlong Huang ◽  
Xiaoyuan Gu ◽  
Xianshang Zeng ◽  
Baomin Chen ◽  
Weiguang Yu ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Inductive Treatment ◽  
Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8029-8029
Author(s):  
Binod Dhakal ◽  
Shruti Sharma ◽  
Svetlana Shchegrova ◽  
Minu Maninder ◽  
Meenakshi Malhotra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Multiparameter Flow Cytometry ◽  
High Dose ◽  
Blood Samples ◽  
Ctdna Analysis

8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here we attempt to evaluate MRD using ctDNA in AHCT recipients with MM. Methods: In this retrospective, single-center study, we analyzed ctDNA MRD in blood samples collected from 28 patients with MM after upfront AHCT. A total of 80 plasma timepoints were available pre and post AHCT with a median follow-up of 92.4 months. Multiparameter flow cytometry (MFC) at 10-4 level was used to assess the MRD from the BM biopsy. Individual bone marrow aspirates or FFPE slides from the time of MM diagnosis and matched normal blood were whole-exome sequenced, and somatic mutations were identified. MRD assessment at 3 months post-AHCT was performed by ctDNA analysis using a personalized, tumor-informed (SignateraTM, bespoke mPCR NGS assay). The prognostic value of ctDNA was evaluated by correlating MRD status with clinical outcomes. Results: Table provides the baseline disease characteristics. Median age was 67 [41-75] years and 16 [57.1%] were males. ctDNA was detectable in 70.8% (17/24) of pre-AHCT, 53.6% (15/28) of ̃3 months post-AHCT, and 39.2% (11/28) of patients during the surveillance phase post-AHCT. Of the 15 ctDNA MRD positive patients, 93.3% (n=14) experienced relapse on follow-up (hazard ratio: 5.64; 95% CI: 1.8-17; p=0.0003). Patients negative for ctDNA at 3 months post-AHCT had significantly superior progression-free survival (PFS) compared to positive (median PFS, 84 months vs. 31 months; p=0.003) The positive predictive value (PPV) for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, and significantly higher than marrow MFC of 68.4%. Conclusions: Our study shows the feasibility that a tumor-informed assay on archival blood samples is predictive of relapse post-AHCT. Future prospective studies with real-time marrow NGS and ctDNA samples are needed to define the role of ctDNA in MM and its prognostic significance.[Table: see text]

scholarly journals Radiographic evaluation of the use of transverse traction device in vertebral arthrodesis for degenerative diseases

2014 ◽  
Vol 13 (1) ◽  
pp. 27-30
Author(s):  
Edgar Takao Utino ◽  
João Paulo Machado Bergamaschi ◽  
Luciano Antonio Nassar Pellegrino ◽  
Ricardo Shigueaki Galhego Umeta ◽  
Maria Fernanda Silber Caffaro ◽  
...  
Keyword(s):  
Evaluation Studies ◽  
Fusion Rate ◽  
Radiographic Evaluation ◽  
Pedicle Fixation ◽  
Degenerative Lumbar Diseases ◽  
Significant Difference ◽  
Traction Device ◽  
Consolidation Rate ◽  
The Stability

OBJECTIVE: Perform radiographic analysis of the use of Transverse Traction Device (DTT) with respect to fusion rate in patients submitted to vertebral arthrodesis for degenerative lumbar diseases. METHODS: We selected x-ray images on anteroposterior, lateral and oblique views and with maximum flexion and extension dynamics of 23 patients submitted to posterolateral arthrodesis of the lumbar spine with a minimum follow-up period of six months. The images were evaluated and classified by the Linovitz's system by two spine surgeons. RESULTS: We evaluated the radiographs of 23 patients after the minimum postoperative period of 6 months and of these, 11 have used DTT. With regard to the consolidation rate, seven patients (63.6%) in the group of DTT were classified as fusion as well as six patients (50%) who were not submitted to the treatment. There was no statistical difference between the groups regarding the consolidation rate. CONCLUSION: The use of transverse traction device in this study showed no significant difference in the rate of consolidation in radiographic evaluation. Studies on the effective participation of this device in the stability of pedicle fixation systems are still lacking in the literature.

Sub-staging specific differences in recurrence-free, progression-free and cancer-specific survival for patients with T1 bladder cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
GuanQiu Chen ◽  
Tao Yang ◽  
Pu Zhang ◽  
Meng-Zhao Zhang ◽  
Bo Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Significance ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Staging System ◽  
Cochrane Library ◽  
Significant Prognostic Factor ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Significant Difference

Abstract Background: The efficiency of the T1 sub-staging system on categorizing bladder cancer (BC) patients into subgroups with different clinical outcomes was unclear. We summarized relevant evidences, including recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS), to analyze the prognostic significance of T1 sub-stage.Methods: Systematic literature searches of MEDLINE, EMBASE and the Cochrane Library were performed. We pooled data on recurrence, progression, and CSS from 35 studies.Results: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated the difference in RFS between T1a sub-stage and T1b sub-stage (HR1.28, 95%CI 1.14-1.43). The significant difference was observed in PFS between the two arms (HR 2.18, 95%CI 1.95-2.44). Worse CSS was found in T1b patients than T1a patients (HR 1.45, 95%CI 1.28-1.64).Conclusions: T1 sub-staging system based on the invasion depth into muscularis mucosae (MM) can be a significant prognostic factor for RFS, PFS, and CSS of patients with T1-BC. Urologists and pathologists are encouraged to work together to give a precise sub-stage classification of T1-BC, and T1 sub-staging system should be a routine part of any histopathological report when possible. Different treatment strategies need to be developed for both T1a-BC and T1b-BC.

The Relationship Between N-Terminal Pro-Brain Natriuretic Peptide Level and Myocardial Performance Index and Their Prognostic Importances in Patients With Acute Myocardial Infarction in Short Term Follow-up

2020 ◽  
Vol 1 (1) ◽  
pp. 12-17
Author(s):  
Mehmet Küçükosmanoğlu ◽  
Cihan Örem
Keyword(s):  
Heart Failure ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ejection Time ◽  
Ventricular Ejection Fraction ◽  
Significant Difference ◽  
The Mean ◽  
The Relationship

Introduction: MPI is an echocardiographic parameter that exibit the left ventricular functions globally. NT-proBNP  is an important both diagnostic and prognostic factor in heart failure. In this study, we aimed to investigate the prognostic significance of serum NT-proBNP levels and MPI in patients with STEMI. Method: Totally 104 patients with a diagnosis of STEMI were included in the study. Patients followed for 30-days and questioned for presence of symptoms of heart failure (HF) and cardiac death. Patients were invited for outpatient control after 30-days and were divided into two groups: (HF (+) group) and (HF (-) group). Results: Totally 104 patients with STEMI were hospitalized in the coronary intensive care unit. Of those patients, 17 were female (16%), 87 were male (84%), and the mean age of the patients was 58.9±10.8 years. During the 30-day follow-up, 28 (27%) of 104 patients developed HF. The mean age, hypertension ratio and anterior STEMI rate were significantly higher in the HF (+) group compared to the HF (-) group. Ejection time (ET) and left ventricular ejection fraction (LVEF) were significantly lower and MPI was significantly higher in the HF (+) group. When the values on day first and  sixth were compared, NT-ProBNP levels were decreased in both groups. There was no significant difference between the two groups in terms of the change in MPI values on the first and sixth days. Multiple regression analysis showed that the presence of anterior MI, first day NT-proBNP level and LVEF were independently associated with development of HF and death. Conclusion: In our study, NT-proBNP levels were found to be positively associated with MPI in patients with acute STEMI. It was concluded that the level of NT-proBNP detected especially on the 1st day was more valuable than MPI in determining HF development and prognosis after STEMI.  

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

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