The Alemtuzumab Treatment of Refractory to Fludarabine Chronic Lymphocytic Leukemia Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4415-4415 ◽  
Author(s):  
Elena Kataeva ◽  
Anatoly Golenkov ◽  
Elena Triphonova ◽  
Iolanta Buravtsova
Keyword(s):  
Flow Cytometry ◽  
Chronic Lymphocytic Leukemia ◽  
Dose Escalation ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Stage Iv ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Level 1 ◽  
High Level

Abstract Abstract 4415 The aim of this study was to explore the efficiency of treatment with Alemtuzumab (A.) of chronic lymphocytic leukemia (CLL) patients (pts) refractory to Fludarabine(F.). Meterials and methods We observed 6 pts (3 male and 3 female). The median age was 56 years old(52-69). 4 of the pts had Rai stage I desease, 1 patient had Rai stage III, 1 had Rai stage IV. We revealed that 4 pts had 17p deletion with high level, 1 patient did not have del 17p, 1 - was not assessed. High level of the expression of CD38+ was determined, the median number was 37,3%(15-82). All pts were pretreated with Chlorambucil, COP, CHOP, FC for 18 months(7-48). All pts were refractory to F. 5 pts received A. monotherapy during median 9 weeks (2-18). Subcutaneous(SQ) A. dose escalation: 3mg-10mg-30mg on days 1,3,5, followed by 30mg Monday, Wednesday and Friday for 17 weeks. 1 patient received 5 courses FluCam(A. 30 mg 1,2,3 days IV after dose escalation 3mg-10mg-30mg, F. 25mg/m2 1,2,3 days). All pts received PCP, herpes and cytomegalovirus(CMV) and fungal prophylaxis as well as CMV viral DNA monitoring. Responses were based on NCI-WG 1996 criteria. Minimal residual disease (MRD) was measured in peripheral blood and bone marrow aspirate using flow cytometry for CD19+/CD5+/CD23+ lymphocytes. Results The efficiency of the treatment of CLL pts was following: 2 pts (33,3%) displayed disease progression(PD) in 2 and 4 weeks of A. monotherapy, 2 pts achived (33,3%) CR in 14 and 16 weeks, 2 pts (33,3%), achived PR, among them 1 patient showed PR after 5 FluCam courses, the other — after 14 weeks of A. monotherapy. At the completion of the study 4 pts (66,6%) had no evidence of MRD by flow cytometry(<0,01%). Conclusion Obtained results showed high effectiveness of A. and acceptable toxity, among resistant to F. CLL pts (66,6% responded), the majoority of them had unfavourable del 17p. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Marked Variability in Reported Minimal Residual Disease Lower Level of Detection of 4 Hematolymphoid Neoplasms: A Survey of Participants in the College of American Pathologists Flow Cytometry Proficiency Testing Program

2015 ◽  
Vol 139 (10) ◽  
pp. 1276-1280 ◽  
Author(s):  
Michael Keeney ◽  
Jaimie G. Halley ◽  
Daniel D. Rhoads ◽  
M. Qasim Ansari ◽  
Steven J. Kussick ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Plasma Cell Myeloma ◽  
Minimal Residual

Context Flow cytometry is often applied to minimal residual disease (MRD) testing in hematolymphoid neoplasia. Because flow-based MRD tests are developed in the laboratory, testing methodologies and lower levels of detection (LODs) are laboratory dependent. Objectives To broadly survey flow cytometry laboratories about MRD testing in laboratories, if performed, including indications and reported LODs. Design Voluntary supplemental questions were sent to the 549 laboratories participating in the College of American Pathologists (CAP) FL3-A Survey (Flow Cytometry—Immunophenotypic Characterization of Leukemia/Lymphoma) in the spring of 2014. Results A total of 500 laboratories (91%) responded to the supplemental questions as part of the FL3-A Survey by April 2014; of those 500 laboratories, 167 (33%) currently perform MRD for lymphoblastic leukemia, 118 (24%) for myeloid leukemia, 99 (20%) for chronic lymphocytic leukemia, and 91 (18%) for plasma cell myeloma. Other indications include non-Hodgkin lymphoma, hairy cell leukemia, neuroblastoma, and myelodysplastic syndrome. Most responding laboratories that perform MRD for lymphoblastic leukemia reported an LOD of 0.01%. For myeloid leukemia, chronic lymphocytic leukemia, and plasma cell myeloma, most laboratories indicated an LOD of 0.1%. Less than 3% (15 of 500) of laboratories reported LODs of 0.001% for one or more MRD assays performed. Conclusions There is major heterogeneity in the reported LODs of MRD testing performed by laboratories subscribing to the CAP FL3-A Survey. To address that heterogeneity, changes to the Flow Cytometry Checklist for the CAP Laboratory Accreditation Program are suggested that will include new requirements that each laboratory (1) document how an MRD assay's LOD is measured, and (2) include the LOD or lower limit of enumeration for flow-based MRD assays in the final diagnostic report.

Comparative Efficacy of First-Line Chemotherapy-Free Combinations in Chronic Lymphocytic Leukemia (CLL): A Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Philip A Haddad ◽  
Nowell Ganey ◽  
Kevin M. Gallagher
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
English Language ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Meta Analysis ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Significant Difference ◽  
Anti Cd20

Introduction: Chronic Lymphocytic Leukemia (CLL) is an incurable B-cell malignancy which disproportionately affects the elderly. Although first-line chemoimmunotherapy (CIT) improved CLL clinical outcomes, recent randomized trials revealed superior outcomes with novel chemotherapy-free combinations (CFC) incorporating anti-CD20 monoclonal antibodies and inhibitors of BTK or Bcl-2. So far, these CFC have not been compared head-to-head. We conducted this network meta-analysis to evaluate their relative efficacy to each other. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of CLL; trials that explored the efficacy of first-line CFC with Obinutuzumab (O), Rituximab (R), Ibrutinib (IB), Acalabrutinib (ACAL), Venetoclax (VEN) compared to standard CIT that included Chlorambucil (CHLOR) with either R or O, Bendamustine+Rituximab, or Fludarabine+ Cyclophosphamide+R; and phase 3 randomized studies reporting responses, progression, death, and adverse (AE) events. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Five studies comprising a total of 2,272 participants were included. When O-based CFC data was analyzed, only ACAL-O had a significant lower relative risk (RR) of progression and death (P&D). There were no significant differences with respect to overall response rates (ORR), complete remission (CR), minimal residual disease (MRD), or grade &gt;3 adverse events (Grd3+) among O-based CFC. When R-based CFC data was analyzed, IB and IB-R were not different with respect to RR of P&D, ORR, CR, MRD, or Grd3+. When the data was analyzed as CFC versus combined CIT, only ACAL-O was found to be significantly superior to other O- and R-based CFC with respect to RR of P&D. ORR and Grad3+ rates of O- and R-based CFC were not significantly different. While ACAL-O, IB-O, and VEN-O had superior CR and MRD rates compared to other CFC, there were no significant differences among each other. Conclusions: This network meta-analysis is the first to compare and rank first-line CFC therapies in CLL. It indicates that ACAL-O has a superior profile having the lowest RR of P&D without significant difference in Grd3+ among CFC. Disclosures No relevant conflicts of interest to declare.

Combination Chemoimmunotherapy with Pentostatin, Cyclophosphamide and Rituximab Shows Significant Clinical Activity with Low Accompanying Toxicity in Previously Untreated B-Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 35-35
Author(s):  
Neil Kay ◽  
Susan Geyer ◽  
Timothy Call ◽  
Tait Shanafelt ◽  
Clive Zent ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Significant Clinical Activity

Abstract BACKGROUND: B-Chronic Lymphocytic Leukemia (CLL) is still uncurable but very powerful new tools are available with the use of chemoimmunotherapy (CIT). Purine nucleoside-based regimens that incorporate rituximab have generated very high levels of overall responses (OR) with significant percentage of those complete responses (CR) in previously untreated CLL. Here we report and update our experience with a phase 2 pentostatin-based CIT regimen for previously untreated CLL as conducted at 2 medical centers. We also studied the association of outcome based on risk stratification parameters and achievement of minimal residual disease. METHODS: Building on prior work of pentostatin in CLL by us (Kay ASH, 2004) and others, we initiated a trial of combined pentostatin (P)(2 mg/m2), cyclophosphamide (C)(600 mg/m2) and rituximab (R)(375 mg/m2) for symptomatic, previously untreated patients (n=65). This PCR regimen is given on a 21-day, 6-cycle schedule. However, the initial cycle of treatment uses thrice weekly rituximab as described by us earlier. In brief, this was rituximab at 100 mg/m2 on day 1, 375 mg/m2 on days 3 and 5 of the first week only. Prophylactic Sulfamethoxazole/Trimethoprim and Acyclovir were given to all patients for 1 year starting on the first cycle of therapy with PCR. All patients were risk stratified using CD38, ZAP-70, immunoglobulin heavy chain variable region gene (IgVH) and FISH panel assessments at entry. RESULTS: These patients were characterized as mostly in high-risk categories. Of 64 evaluable patients, 34 (53%) were high Rai risk (stage 3–4), 71% were non mutated for the IgVH gene, 34% were CD38+ and 34% were ZAP-70+. Thirty patients (52%) had one FISH anomaly, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs, and no major infections. NCI Working Group Criteria Responses occurred in 58 (91%) with 26 (41%) complete responses (CR), 14 (22%) nodular partial responses (nodular PR), and 18 (28%) partial responses (PR) patients. Outcome for all 64 patients demonstrates a median progression-free survival of 32.6 months. Importantly, no high risk factor (i.e., age, FISH, IgVH status, CD38+, ZAP-70+) except for del (17p) defect (n=3) precluded attaining a CR or NPR. In contrast, we found this regimen was equally effective in young vs. elderly (>70 yrs) patients and in del(11)(q22.3) vs. other favorable prognostic FISH factors. Examination of outcome among CR and nodular PR patients for PFS by flow cytometry status (negative vs. positive, i.e., ≤ 1 % CD5+/CD19+ vs. ≥ 1 % CD5+/CD19+) demonstrated improvement in progression free survival for patients who attained flow cytometry negativity (p = 0.009). Conclusion: This novel regimen of pentostatin, cyclophosphamide and rituximab for previously untreated CLL demonstrated significant clinical activity despite poor risk-based prognoses with minimal toxicity in terms of bone marrow suppression and/or infections. The additional feature of this approach is the ability to have durable responses for all age groups and even CLL patients with a del(11)(q22.3).

CD23 Receptor Positivity Has No Prognostic Implication in Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4397-4397
Author(s):  
Jahan Aghalar ◽  
Charles Chu ◽  
Rajendra N Damle ◽  
Che-Kai Tsao ◽  
Nina Kohn ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Markers ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Mutation Status ◽  
Percent Positivity ◽  
Cd23 Expression

Abstract Abstract 4397 BACKGROUND Chronic Lymphocytic Leukemia (CLL) phenotypically expresses CD23, although the percentage of positive cells measured by flow cytometry is variable. We sought to analyze whether the percent of CD23 positive cells in the CLL clone correlates with time to treat (TTT), overall survival (OS) and prognostic markers CD38, ZAP-70, and IGHV mutation status. METHODS We retrospectively analyzed the flow cytometry data of 332 CLL patients on the gated population of cells that were CD5 and CD19 positive. Percentage positivity for CD23, CD38, and ZAP-70 was noted. CD38 and ZAP-70 were considered positive at cut-offs of >= 30% and >=20%, respectively. CD23 was considered negative at <30% and positive at >= 30%. IGHV sequence was determined from cDNA and then compared to germline to assess mutation status using IMGT/V-QUEST. The distributions of time from diagnosis until start of treatment and overall survival were stratified by CD23 positivity, estimated using the product limit method, and compared using the log rank test. Those who had expired without treatment or were alive and not treated at this time point were censored in the TTT analysis. Those who were still alive were censored in the OS analysis. Associations of CD23 positivity with IGHV mutation status, ZAP-70, and CD38 positivity were examined using the chi-square test. RESULTS Out of 332 patients, 25 had diminished CD23 expression (<30%) whereas 307 had normal CD23 expression (>30%). There was no difference in time until start of treatment or overall survival based on CD23 %positivity. CD23 %positivity showed no associations with IGHV mutation status, ZAP-70 or CD38 positivity. CONCLUSION CD23 percent positivity has no prognostic significance in CLL. There is no correlation between CD23 percent positivity and poor prognostic markers such as CD38, ZAP-70, or IGHV mutation status. Disclosures: No relevant conflicts of interest to declare.

Chronic Lymphocytic Leukemia Treatment in México: Up to Half Patients May Not Requiere Treatment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Luisa Fernanda Sánchez-Valledor ◽  
Carmina Alejandra Córdova-Ramírez ◽  
Gilberto David Elias-de-la-Cruz ◽  
Montserrat Rivera-Álvarez ◽  
Antonio Cruz-Mora ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Stage Iv ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Malignant Cells ◽  
Simplified Approach ◽  
Anti Cd20

Introduction Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm which represents the most frequent hematologic malignancy in Caucasians. Every year, there are15,000 new diagnoses and 5000 CLL deaths in the United States. Its prevalence in México and other non-Caucasian populations is substantially lower and the clinical course of CLL patients has been described to be less aggressive Methods All consecutive patients seeking medical care after 1983 in our institution as a result of CLL and followed for at least 3 months were entered in the study. The study was approved by the institutional review board. The treatment of patients was withheld in: (a) Persons with CLL Rai stage 0 or 1, until progression; (b) Persons with CLL Rai stage 2-4, with a negative expression of ZAP-70 until progression. Progression was defined by: Anemia, thrombocytopenia, massive symptomatic or progressive splenomegaly and or adenopathy, progressive lymphocytosis (&gt;50% increase in two months or lymphocyte doubling timeless than 6 months), autoimmune hemolytic anemia not responding to standard therapies, or constitutional symptoms: Weight loss greater than 10% in 6 months, unexplained night sweats or unexplained fever for 2 or more weeks. Refractoriness of the disease was defined as progression despite treatment for a minimum of 3 months. Results Among 98 patients with CLL who were accrued in the study between 1983 and 2019, 49 (50%) were followed for three or more months and accordingly, entered in the study. Median follow up time of the patients is 61 months (95% CI 46.1-75.8). There were 15 females and 34 males, the median age was 65 years (range 23-86). According to the Rai staging system, there were 24 stage 0, 7 stage I, 8 stageII, 0 stage III and 10 stage IV; 80% of patients were identified in stages 0-II. In 28 patients a complete immune phenotype of the malignant cells was analyzed: 89% of patients were ZAP-70 negative (ZAP expression in less than 20% of malignant cells), 79% expressed CD5, 100% CD19 and 86% CD23. Three patients were born in European countries, whereas 6 had an immediate European ancestor, indicating that a Caucasian background was identified in 9/49patients (18%). There were no instances of T-cell CLL. Median OS for all the patients has not been reached, being above 247 months (20 years). The OS of patients given or not any treatment was not statistically different (p= 0.09). It is clear that patients who needed treatment did worse than those not needing treatment but the differences were not significant. Patients with advanced stages (III and IV) had a worse outcome than those in early stages. Median OS for patients given no treatment at all has not been reached and is above 247 months; median OS for patients given CP was 115 months, median OS for those given FC has not been reached and is above 132 months, whereas median OS for persons given FCR has not been reached, being above 136 months; all these differences are not statistically significant. Eight of 49 patients were found to be refractory to treatment; they were receiving CP (5 cases); FC (2 cases) and FCR (one case); these refractory patients were given, FCR (7 cases) and rituximab/ifosfamide/carboplatin/etoposide (one case). No patient had to be given cladribine, pentostatin, alemtuzumab (anti-CD52), bendamustine, ofatumumab (anti-CD20), obinutuzumab (anti-CD20), lenalidomide, ibrutinib nor idelalisib. Conclusion In the era of novel anti-CLL drugs, we have found that the clinical course of these patients in México seems to be less aggressive than in Caucasian populations and that, in consequence, circa 50% of them do not need any treatment at all. In those needing treatment, the use of a simplified approach and taking advantage of improved supportive care measures, acceptable results are obtained even if all of the new CLL drugs are not employed. These observations may be critical in developing countries, where the cost of the drugs will continue to be a major factor in choosing therapies. Disclosures No relevant conflicts of interest to declare.

The Treatment of Complicated and High Risk Chronic Lymphocytic Leukemia (CLL) with Fludarabine, Cyclophosphamide and Rituximab (FCR).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5038-5038 ◽  
Author(s):  
Vijaya Donthireddy ◽  
Muhammad S. Shurafa ◽  
Murad Saleh ◽  
Ginny Kamboj ◽  
Ding Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Thrombocytopenia ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Massive Lymphadenopathy ◽  
Initiation Of Therapy ◽  
Effective Treatment Regimen

Abstract Between November 2000 and November 2004, we treated 11 patients with the FCR regimen for complicated CLL. The median age was 64 years (51–80 years) and the median number of prior regimens received was 1(0–4). Median number of FCR cycles delivered was 4 (2–6). Four patients were treated due to active autoimmune hemolytic anemia (AIHA), three patients due to massive lymphadenopathy, two patients for short lymphocyte doubling time, one patient for active AIHA and immune thrombocytopenia and one patient for progressive splenomegaly. Two patients received only 2 cycles of FCR due to prolonged pancytopenia secondary to hypoplastic bone marrow. Four of the patients with AIHA had prior splenectomies. Overall response rate, according to NCIWG criteria, was 100% including the patients who had received only 2 cycles. One patient achieved a complete remission, seven patients achieved nodular partial remissions and three achieved partial remissions. Among the 7 patients with nodular PR’s, 4 had no evidence of residual CLL by flow cytometry and are continuing to be in remission at a median follow up of 53 months. The other 3 patients with nPR who had evidence of disease by flow cytometry relapsed at a median of 23 months (16–33 months). The patient who had a CR by NCIWG criteria, still had evidence of disease by flow cytometry and relapsed at 35 months. All patients with AIHA and immune thrombocytopenia achieved a remission of their autoimmune processes, including those who failed splenectomy. Grade 3–4 neutropenia, thrombocytopenia and anemia occurred in 8, 2 and 2 patients respectively. The median progression free interval was 33 months (9+ to 54 m) and the overall survival was 56 months (9+ to 56m). Four patients had expired at the time of this report due to progression of CLL(1), sepsis while still in remission(1), high grade transformation and subsequent sepsis(1) and complications of allogeneic transplant(1). Cytogenetic remissions were achieved in 7/9 patients. Three of them continue to be in remission at the time of this report with a median follow up of 53 months since initiation of therapy. Conclusion: FCR is an effective treatment regimen for CLL associated AIHA, even after failing splenectomy and can result in high response rates and prolonged remissions. Flow cytometry remission seems to correlate with prolonged disease free survival in patients achieving nodular partial remissions according to the NCIWG criteria. We suggest treatment with FCR until elimination of minimal residual disease by flow cytometry irrespective of histopathological remission.

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