Background: Outcomes of therapy for adult population diagnosed with acute lymphoblastic leukemia (ALL) remain unsatisfactory. Chemotherapy with or without bone marrow transplant (BMT) is the mainstay of treatment. We sought to describe the outcomes of chemotherapy in our population of adults with ALL who were not eligible for bone marrow transplant due to socio-economic reasons. Methods: Data from 50 patients (pts) with ALL over an 8-year period were studied as a retrospective cohort for clinical presentation, response, remission duration and long-term survival. Clinical and survival data were analyzed via Student’s T test and Fisher’s exact test. Time to relapse was analyzed with Kaplan-Meier life table analyses and Log Rank test. Results: There were 16 (32%) women and 34 (68%) men diagnosed with ALL. Median age at diagnosis was 31 years. Hispanics were the majority group with 27 pts (54%), African Americans 11 (22%), Caucasians 8 (16%), and Asian 4 (8%). B precursor ALL was present in 39 pts (78%), T precursor ALL in 8 (16%), and Burkitt’s leukemia in 3 (6%). Cytogenetics were available in 42 pts (84%): 29 pts (58%) were intermediate risk, 12 (24%) poor risk, and 1(2%) good risk. Ph chromosome was present in 6 pts (12%). A WBC above 30,000/dL was seen in 13 pts (25.49%). Myeloid markers were present in 9 (17.64%), CD10 in 45 (88.23%), and CD34 in 34 (66.6%) pts. Four pts (7.84%) had CNS disease at presentation and 3 (5.9%) had mediastinal disease. Based on age, WBC count, cytogenetics, and CNS disease at diagnosis, there were 28 high-risk pts (56%) and 22 standard-risk pts (44%). Majority of pts 38 (76%) received a 4-drug induction chemotherapy (BFM protocol). Hyper-CVAD, and CALGB protocols were used in 6 pts each (12%). A total of 42 pts (84%) achieved remission after first induction chemotherapy. There were 3 deaths (6%) and 5 (10%) nonresponders (NR). After the induction protocol, 19 pts remained in remission but 21 pts (50%) relapsed. Median time to first relapse (TTR) was 12 months. Relapsed pts were re-induced with 2nd line chemotherapy: Hyper-CVAD regimen in 10 pts (47.6%), BFM protocol in 4 (19%), and 33% with other regimens. Eleven pts (52.3%) entered a 2nd remission, 3 died, and 7 NR. Out of 11 pts who achieved a second remission, 5 pts later relapsed, 1 was still in remission at the last follow up, 2 underwent BMT and 3 were lost to follow up. TTR was analyzed according to age, gender, ethnicity, immunophenotype, cytogenetics, WBC count, presence of CD10, CD34, myeloid markers and induction protocol and no significant differences were found. Median overall survival was 16 months (range 1–97 months). Significant differences in survival were found with regards to cytogenetics (poor vs. intermediate risk, p= 0.027), presence of Ph chromosome (p= 0.0002), CNS disease at diagnosis (p= 0.0046), and response to first chemotherapy (p= 0.0032). There were no differences in overall survival according to age, gender, Hispanics vs. other ethnic groups, immunophenotype (B vs. T ALL), WBC count, presence of CD10, CD34, and myeloid markers. Also, the choice of chemotherapy regimen did not impact survival significantly. Conclusions: This cohort of patients revealed a predominance of younger male adults (median age 31 years), Hispanics (54%) and high-risk disease (56%). Remission rate after induction was 84% and early death rate (6%), comparable to those reported in the literature. 50% of responders relapsed after a median TTR of 12 months. No factors were found to impact the TTR significantly. Median survival was 16 months lower than historical cohort (30 months). Cytogenetics, Ph +, CNS disease at diagnosis and response to chemotherapy had a significant impact on survival but not on TTR. More investigation of factors which affect long-term outcome in minority population is needed.
Introduction: Imatinib (STI571/ Gleevec) is a tyrosine kinase inhibitor that functions by blocking the binding of ATP to the bcr-abl tyrosine kinase, inhibiting its activity and preventing myeloid proliferation, a characteristic of CML. We report our experience with imatinib use in a minority patient population. Methods: Data from 67 patients (pts) with CML treated at Cook County Hospital, Chicago, Illinois over a 4 year period were collected. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student’s T test and categorical data via Fisher’s Exact test. Results: 57 pts with complete data [mean age at diagnosis 42.8 yrs, range 19–72 yrs, 46 (80.7%) males and 11 (19.3%) females] were identified and analyzed as a retrospective cohort. 41 pts (71.9%) were between 30 and 60 yrs of age and 17 pts (29.8%) had ≥ 1 major comorbidity at presentation. 28 (49.1%) were African American (AA), 4 (7%) Asian, 5 (8.8%) Eastern European, 17 (29.8%) Hispanic, and 3 (5.3%) Middle Eastern. 50 pts (87.7%) were in chronic phase, 5 (8.8%) in accelerated phase, 2 (3.5%) in blast phase, 2 (3.5%) had granulocytic sarcomas and 5 pts (8.8%) had second malignancies at presentation. 54 pts (94.7%) were started on 400mg of imatinib. 19 pts (33.3%) had imatinib-related toxicities including skin rash, cytopenias and nausea. 17 pts (29.8%) were non-compliant with imatinib therapy. AA pts were as old as the non-AA pts [44.8 ± 12.6 yrs vs 40.9 ± 13.8 yrs, p 0.27]. Non-AA pts were predominantly male. Following imatinib therapy a hematologic response (HR) was noted in 45.7± 54.6 days (d) in AA vs 31.3 ± 23.9 d in non-AA (p= 0.27), a major cytogenetic response (MCR) in 351 ± 342.6 d in AA pts vs 289±132.7 d in non-AA (p=0.58) and a complete cytogenetic response in 664±265.1 d in AA vs 642±292.5 d in non-AA pts (p=0.87). 11 AA pts failed imatinib therapy vs 8 non-AA pts. These pts were then subjected to imatinib dose escalation (600mg or 800mg) with only 4 pts in the AA group attaining MCR and 1 pt in the non-AA group attaining CCR. 4 AA pts then received Dasatanib and 2 went on to Allogeneic Stem Cell Transplant (ASCT) and 3 pts in the non-AA group received Nillotinib or Dasatanib and 2 went on to ASCT. There were 3 deaths in the AA group vs 1 in the non-AA group. Conclusion: In this primarily minority-based cohort there appears to be no significant difference in the age or gender distribution of the AA or non-AA pts although there appeared to be a male preponderance amongst the non-AA pts. The ethnic background does not appear to affect the time to significant hematologic response, major cytogenetic response or complete cytogenetic response to imatinib therapy in the AA or non-AA pts. Since the number of patients is small, definitive conclusions in either cohort cannot be made. Further investigation in minority patients is warranted.
BACKGROUND: Chronic lymphocytic leukemia (CLL) is noted to exhibit male predominance, median age of 65 years at diagnosis and variable survival. Little data exist however regarding the characteristics of CLL in the U.S. minority population. METHODS: Data from 72 patients (pts) with CLL were collected from the primarily minority population served by Cook County Hospital, Chicago, Illinois over a 6 year period, and analyzed for clinical, presentation and prognostic characteristics and long-term survival. Continuous data were analyzed via Student’s T test and categorical data via Fisher’s Exact test. Survival was ascertained via Social Security Death Index query and analyzed using Kaplan Meier life-table analyses. RESULTS: 72 pts [age at diagnosis 58.4 ± 12.1 yrs, range 31–94 yrs, 45 (62.5%) males, 27 (37.5%) females] were identified and analyzed as a retrospective cohort. 16 pts (22.2%) were < 50 yrs of age and the majority of pts (53, 73.6%) had ≥ 1 major medical comorbidity at presentation. 40 (55.5%) were African American (AA), 18 (25%) Caucasian, 6 (8.3%) Hispanic, 4 (5.5%) Middle Eastern, and 4 (5.5%) Asian. Distribution by Rai stage at diagnosis was as follows: 16 (22.2%) pts Stage 0, 17 (23.6%) Stage 1, 6 (8.3%) Stage 2, 16 (22.2%) Stage 3, 16 (22.2%) Stage 4 and 1(1.4%) Richter transformation. 17 pts (23.6%) were low risk, 24 (33.3%) were intermediate risk and 31 (43.1%) were high risk (HR). Of 65 pts in whom prognostic data were available 46 (70.8%) pts had 1 or more HR features of which 25 (54.3%) were AA. Poor prognosticators included clinical stage 3 and 4 (43.1%), beta2m > 5.0 (4%), diffuse involvement of BM (36.4%), ZAP-70 positivity (20%), CD38 positivity (15.7%) and poor cytogenetic profile (del 11q / del 17q, 23.7%). CLL-associated complications included AIHA in 8 (11.1%) pts, (3/8 Coomb’s positive), ITP in 1(1.4%) pt, hypogammaglobinemia in.20/27 (74.1%) tested pts, CLL transformation to DLBCL (Richter) in 1(1.4%) pt, and second malignancies in 6 (8.3%) pts. AA pts, comprising the largest ethnic subgroup, were significantly older than non-AA pts (60.9 ± 12.9 yrs vs 55.3 ± 10.5 yrs, p<0.0478) and were more likely to have >1 medical comorbidity than non- AA pts (55.6% vs 25.0%, p=0.014). Both advanced stage at presentation (Rai 3 and 4, AA:42.5% vs non-AA:46.9%, p=0.812) and high-risk profile (AA:67.5% vs non-AA:55.9%, p=0.34) were comparably distributed between AA and non-AA pts. A modest difference was noted between AA and non-AA pts in the likelihood of receiving treatment (52.5% vs 68.8%, p=0.23) however survival at mean follow-up of 26.5 ± 20.7 months was similar (90% vs 87.5%, p=1.0). CONCLUSIONS: The primarily minority-based, public health system patient cohort analyzed in this observational study were somewhat younger than published historical control populations at the time of CLL diagnosis. African American pts while generally older and noted to have more comorbidities, had comparable disease stage and risk profiles at presentation as non-African American pts. The numerical disparity between proportions of AA vs non-AA pts treated did not appear to impact survival in this analysis. Further investigations of diagnostic, prognostic and healthcare disparities in the underserved minority population, are warranted.
Background: Fludarabine based chemotherapy has been increasingly used in the treatment of chronic lymphocytic leukemia (CLL). We describe our experience with fludarabine combination chemotherapy (mainly FCR-fludarabine, cyclophosphamide, rituximab) in a minority predominant population with CLL. Methods: 35 patients (pts) with progressive or advanced CLL treated with fludarabine based regimens at Cook County Hospital, Chicago, IL over an 8-year period were studied as a retrospective cohort for clinical response, remission duration and long-term survival. Clinical and survival data were analyzed via Student’s T test and Fisher’s exact test. Time to progression was analyzed with Kaplan-Meier life table analyses and Log Rank test. Results: Twenty out of 35 pts (57.14%) received fludarabine combination therapy as initial treatment (19 FCR, 1 FC) and 15 pts (42.85%) at relapse (12 FCR, 3 FCR/alemtuzumab). Eight pts had previous exposure to fludarabine. Median time to treatment was 17 months. Fourteen pts (40%) were women, and 21 pts (60%) men. Median age at treatment was 58 years. African Americans were the predominant group with 23 pts (65.7%), Caucasian 8 (22.9%), Hispanics 3 (8.6%), and Asian 1 (2.9%) pts. According to Binet stage at diagnosis, 6 pts (17.1%) were stage A, 16 (45.7%) stage B, and 13 (37.1%) stage C. Performance status was 0 in 12 pts (34.3%), and 1 in 23 (65.7%). CD 38 was present in 9 pts (25.7%) and Zap-70 in 11 pts (31.4%). A WBC above 100,000/dL was seen in 16 pts (45.71%) and the median absolute lymphocyte count was 72,900/dL. Lymphocyte doubling time was less then 6 months in 18 pts (51.4%). Seven pts (20%) had prolymphocyte counts between 10–20%. Data for FISH studies was available in 28 pts (80%) and revealed del 11 in 5 pts, del 13 in 8 pts, del 17 in 1, trisomy 12 in 5 pts and 9 pts had normal cytogenetics with negative FISH results. Majority of pts 19 (54.28%) received 6 cycles of chemotherapy. Complete clinical response (CR) was seen in 19 pts (54.3%), partial response (PR) in 11 (31.4%) for an overall response rate of 30 pts (85.7%). There were 3 (8.6%) nonresponders (NR) and 2 pts died (5.7%). Pts with CR were compared to NR and pts with PR. There was no statistically significant difference in response according to age, gender, ethnicity or stage at diagnosis. A borderline significant decrease in CR rate with increasing number of comorbidities (p=0.055) was observed. Previous exposure to fludarabine and number of prior therapies did not impact response significantly. Median duration of follow up was 44 months. Median time to tumor progression (TTP) was 16 months. TTP was analyzed with regards to age, gender, ethnicity, stage, number of comorbidities and no significant differences were found. Also no differences in CR rate or TTP according to flowcytometry (CD38, Zap-70) or genetic tests were found. Neutropenia G3 and G4 was noted in 16 pts (45.71%) with neutropenic fever in 7 pts (20%), and infections in 6 pts (17.14%). Severe anemia and thrombocytopenia was seen in 13 pts (37.14%) and 6 pts (17.1%) respectively. Infusion reactions were observed in 8 pts (22.8%), mainly rigors/chills G1. Therapy was discontinued in 11 pts (31.4%) because of severe infection in 3, intractable cytopenias in 6, death and compliance with 1 patient each. Nineteen (54.2%) pts had delays in chemotherapy mainly due to cytopenias 10 pts, infection 3 pts, neutropenic fevers 2 pts, and Coombs positive hemolytic anemia 1 pt. Prophylactic antibiotic prophylaxis was given in 24 pts (68.75%) and all patients who developed neutropenia received support with growth factors. Conclusions: Our complete clinical response rate to fludarabine combination therapy (FCR) was similar to that previously reported. No statistically significant differences in CR and TTP were found according to age, gender, ethnicity, stage, previous exposure to fludarabine, flowcytometric and genetic parameters were found. A borderline significant decrease in CR rate with increasing number of comorbidities (p=0.055) was observed. In our study there was a high incidence of neutropenia, neutropenic fever and infections that lead to treatment delays in 42.85% and discontinuity in 25.71% of pts despite prophylactic use of antibiotics. Our number of patients does not allow for more definitive conclusions and more studies are needed to address the efficacy and tolerability of fludarabine based regimens in CLL.
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