Ethnic Disparities and Their Association With Outcomes In Chronic Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2917-2917 ◽  
Author(s):  
Sikander Ailawadhi ◽  
Dongyun Yang ◽  
Wendy Cozen ◽  
Asher Chanan-Khan
Keyword(s):  
Survival Analysis ◽  
Chronic Myeloid Leukemia ◽  
Ethnic Minorities ◽  
Myeloid Leukemia ◽  
Significant Interaction ◽  
Age Groups ◽  
Age At Diagnosis ◽  
Investigational Product ◽  
Hispanic Patients ◽  
Race Ethnicity

Abstract Background Outcomes for patients with chronic myeloid leukemia (CML) have improved in recent years. Nonetheless, survival disparities persist between various patient subgroups. There have been limited reports of ethnic variations in CML outcomes, with limited data on ethnic minorities (Hispanics and Asians), who are the fastest growing ethnic subgroups in the Unites States. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of CML patients, with a specific focus on various ethnicities. Methods SEER 17 Registry data (1973-2010) was utilized. Adult (>18 years) patients with confirmed diagnosis of CML were eligible. To avoid bias of under representation by ethnic minorities, analysis was restricted to patients with a diagnosis date of 1992 or later (SEER expansion). Cases that received a diagnosis at death certificate/autopsy, no follow-up records, or lacking age at diagnosis, sex, or race/ethnicity documentation were excluded. Cox proportional hazards models, adjusted for confounding variables, were used to evaluate association between patient characteristics and overall survival (OS). All statistical tests were two-sided with a significance level of 0.05, utilizing the SAS software (v9.2). Results The final analysis included 10,356 CML patients (5,943 males; 57.4%, 4,413 females; 42.6%). Age group cohorts included: 18-44 years (2,592; 25%), 45-54 years (1,706; 16.5%), 55-64 years (1,817; 17.6%), 65-74 years (1,876; 18.1%), and ≥75 years (2,365; 22.8%). Patients were stratified by race/ethnicity: White (7,292; 70.4%), African-American (AA) (1,143; 11%), Hispanic (1,163; 11.2%), Asian (697; 6.7%), and Native American (61; 0.6%). For survival analysis, Native Americans were excluded due to their small numbers. Patients were also stratified based on year of diagnosis (1992-1999, 2000-2004 and 2005-2010) to study the impact of evolving therapeutics on CML outcomes. Median age at diagnosis was significantly different among ethnicities (p<0.001) with Hispanics the youngest (47 years) and Whites the oldest (63 years) (Figure 1). There were more Hispanic and AA CML patients reported in recent years in the database than those in 1992-1999 or 2000-2004 (p<0.001). Survival analysis revealed that for all patients, females had a significantly better median OS than males (7.8 years vs. 6.4 years; p<0.001). Among the different age cohorts, median OS got progressively worse with increasing age at diagnosis (p<0.001), with a median OS of 15+ years in 18-44 year cohort vs. 2.3 years in patients ≥75 years. Patients diagnosed more recently had a better median OS (1992-1999: 4.5 years vs. 2000-2004: 7.7 years vs. 2005-2010: 9.8 years; p<0.001). AA had the worst median OS among all ethnicities, which was significantly worse than Whites (reference) (5.8 years vs. 7.4 years; p<0.001). Asians had a median OS of 6.4 years and Hispanics 6 years. In a multivariate model using race, age at diagnosis, year of diagnosis, sex and marital status, a significant interaction was noted between year of diagnosis and race, with all racial subgroups showing improvement in 5-year survival in more recent time periods (p=0.001) (Figure 2). A significant interaction was also noted between year of diagnosis and age, with a progressive improvement in 5-year survival noted across all age groups in more recent years (p<0.001) (Figure 3). Conclusions We present a population-based study of outcomes in CML with the largest representation of ethnic minorities reported so far. We noted a higher number of AA and Hispanic patients reported to the SEER database in recent years. Hispanic patients had a significantly younger age at diagnosis, which could mean longer treatment duration over the lifetime of a patient. AA patients had the worst median OS among all ethnicities, although all ethnicities and age groups were noted to have progressive improvement in outcomes in more recent years of diagnosis. The incremental benefit in outcomes was seen most for Asians and least for Whites. These results will help in better understanding of ethnic influences on disease biology and clinical behavior as well as optimal triaging of healthcare resources. Disclosures: Off Label Use: The abstract shows scientific information on SAR245409 which is an investigational product developed by Sanofi. This investigational product is not approved by any health authority for any indication.

Educational Session: Managing Chronic Myeloid Leukemia as a Chronic Disease

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Andreas Hochhaus
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Treatment Options ◽  
Age Groups ◽  
Continuous Treatment ◽  
Symptomatic Therapy ◽  
Therapeutic Success

Abstract Elucidation of the pathogenesis of chronic myeloid leukemia (CML) and the introduction of tyrosine kinase inhibitors (TKIs) has transformed this disease from being invariably fatal to being the type of leukemia with the best prognosis. Median survival associated with CML is estimated at > 20 years. Nevertheless, blast crisis occurs at an incidence of 1%-2% per year, and once this has occurred, treatment options are limited and survival is short. Due to the overall therapeutic success, the prevalence of CML is gradually increasing. The optimal management of this disease includes access to modern therapies and standardized surveillance methods for all patients, which will certainly create challenges. Furthermore, all available TKIs show mild but frequent side effects that may require symptomatic therapy. Adherence to therapy is the key prerequisite for efficacy of the drugs and for long-term success. Comprehensive information on the nature of the disease and the need for the continuous treatment using the appropriate dosages and timely information on efficacy data are key factors for optimal compliance. Standardized laboratory methods are required to provide optimal surveillance according to current recommendations. CML occurs in all age groups. Despite a median age of 55-60 years, particular challenges are the management of the disease in children, young women with the wish to get pregnant, and older patients. The main challenges in the long-term management of CML patients are discussed in this review.

Efficacy and Tolerability of Bosutinib and Imatinib in Older Versus Younger Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia–BELA Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4442-4442 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Tim H Brümmendorf ◽  
Dong-Wook Kim ◽  
Irina Dyagil ◽  
Hagop M Kantarjian ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Age Groups ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Kaplan Meier ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 4442 Bosutinib (BOS) is an orally active, dual Src/Abl kinase inhibitor with activity and manageable toxicity in the phase 3 BELA trial of patients (pts) with newly diagnosed (≤6 mo) chronic phase (CP) chronic myeloid leukemia (CML). The current analysis of the BELA trial summarizes the activity and tolerability of BOS 500 mg/d and imatinib (IM) 400 mg/d among older (≥65 y; BOS n = 30; IM n = 27) versus younger pts (<65 y; BOS n = 220; IM n = 225). Sokal risk scores were balanced between treatment arms but, as expected, higher among older pts (4% low; 72% intermediate; 25% high) versus younger pts (39% low; 44% intermediate; 17% high). Minimum follow-up duration was 24 mo. BOS was discontinued by 37% of pts (57% older vs 35% younger; P = 0.023); difference between age groups was primarily due to adverse events (AEs; 39% vs 22%; most commonly increased alanine aminotransferase [ALT]). IM was discontinued by 27% of pts (35% older vs 28% younger; P= 0.496); disease progression was the primary reason. In the intent-to-treat population, cumulative rate of complete cytogenetic response (CCyR) by 24 mo in older/younger pts was 70%/80% on BOS and 78%/80% on IM. Median time to CCyR was 24.0 wk for older versus 12.7 wk for younger pts on BOS and 24.4 wk versus 24.7 wk on IM; in younger pts CCyR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a CCyR, 57%/79% on BOS and 76%/85% on IM were still on treatment and retained their CCyR as of the data cutoff. Cumulative rates of major molecular response (MMR) by 24 mo in older/younger pts were 53%/60% on BOS and 48%/49% on IM. Median time to MMR was 48.1 wk for older versus 48.0 wk for younger pts on BOS and 60.6 wk versus 84.1 wks on IM; for younger pts MMR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a MMR, 63%/84% on BOS and 92%/89% on IM were still on treatment and retained their MMR as of the data cutoff. Kaplan-Meier event-free survival in older/younger pts at 2 y was 100%/91% on BOS and 81%/88% on IM. Kaplan-Meier on-treatment transformation to accelerated/blast phase CML by 2 y was 0% for older and 2% (4 transformations) for younger pts on BOS (4 total), and 9% (2 transformations) for older and 5% (11 transformations) for younger pts on IM (13 total). Kaplan-Meier overall survival in older/younger pts at 2 y was 100%/97% on BOS and 92%/95% on IM. The majority of deaths were due to disease progression (BOS, n = 6; IM, n = 10); few deaths due to AEs on BOS (n = 1) or IM (n = 2) were reported, none treatment related. BOS was associated with higher rates of gastrointestinal TEAEs, elevated ALT and aspartate aminotransferase (AST), and pyrexia; IM was associated with higher rates of musculoskeletal TEAEs and edema (Table). Rates of common TEAEs were generally similar or higher among older pts. Pleural/pericardial effusion occurred in 6 (21%) older pts (3/6 with treatment-related events; median event duration, 36.5 d) versus 5 (2%) younger pts (all with treatment-related events) on BOS, and in no IM pts. Overall grade 3/4 TEAEs were more frequent among older pts on both BOS and IM, as was dose modification (Table). Grade 3/4 lab abnormalities of elevated ALT (BOS, 18% older/24% younger; IM, 4% each) and AST (BOS, 7%/12%; IM, 4% each) were more frequent with BOS versus IM, but similar between age groups. Grade 3/4 lab abnormalities of neutropenia were more frequent with IM (23% older/22% younger) versus BOS (11% each) regardless of age; grade 3/4 anemia (6%-14%) and thrombocytopenia (14%-23%) were generally similar regardless of age or treatment arm. In conclusion, BOS demonstrated activity in both older and younger pts with newly diagnosed CP CML. Although the frequency of certain toxicities as well as treatment discontinuations due to TEAEs was higher among older pts, the toxicity profile of BOS remained manageable and distinct from that of IM regardless of age. Event, % BOS IM ≥65 y (n = 28) <65 y (n = 220) ≥65 y (n = 26) <65 y (n = 225) Non-hematologic TEAEsa     Diarrhea 86 68 46 22     Rash 36 22 27 18     Nausea 36 32 31 37     Vomiting 32 32 19 15     Dyspnea 32 5 12 3     Pyrexia 29 17 4 13     Elevated ALT 29 32 15 8     Elevated AST 25 27 15 8     Elevated lipase 25 12 19 10     Headache 21 12 8 12     Asthenia 21 5 4 7     Dyspepsia 14 6 23 5     Muscle spasms 14 3 35 21     Periorbital edema 7 <1 35 12 Any grade 3/4 TEAE 89 65 73 56 Dose reduction due to AE 64 40 42 18 Dose interruption due to AE 89 63 69 42 Treatment discontinuation due to AE 39 22 8 9 All treated pts were included in the safety analyses. a Includes TEAEs reported for ≥20% of older or younger pts. Disclosures: Gambacorti-Passerini: Pfizer Inc: Consultancy, Research Funding; Novartis, Bristol Myer Squibb: Consultancy. Brümmendorf:Bristol Myer Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Patent on the use of imatinib and hypusination: Patents & Royalties. Kim:BMS, Novartis, Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Pfizer Inc: Research Funding. Pavlov:Pfizer Inc: Employment, Equity Ownership. Gogat:Pfizer Inc: Employment, Equity Ownership. Duvillie:Pfizer Inc: Employment. Shapiro:Pfizer Inc: Employment, Equity Ownership. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding.

scholarly journals Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008

2011 ◽  
Vol 29 (18) ◽  
pp. 2514-2520 ◽  
Author(s):  
Magnus Björkholm ◽  
Lotta Ohm ◽  
Sandra Eloranta ◽  
Åsa Derolf ◽  
Malin Hultcrantz ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Large Population ◽  
Age Groups ◽  
Relative Survival ◽  
The Elderly ◽  
Population Based ◽  
Population Based Study ◽  
First Line Therapy

Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% Cls) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.

Chronic myeloid leukemia incidence trends among Caucasians in the United States.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17005-e17005
Author(s):  
Rakesh Mandal ◽  
Binay Kumar Shah
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Incidence Rate ◽  
Myeloid Leukemia ◽  
Age Groups ◽  
The United States ◽  
Incidence Rates ◽  
Background Information ◽  
Incidence Trends ◽  
Caucasian Women ◽  
Adjusted Incidence

e17005 Background: Information on trend of Chronic Myeloid Leukemia (CML) incidence rate is scant. This study was conducted to evaluate the time trends of CML incidence rates among Caucasians in the U.S. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to extract annual age-adjusted incidence rates of CML from 1973-2008 for <60yr and >60yr age groups classified by gender. Trends of incidence rates were evaluated using the National Cancer Institute’s Joinpoint Regression Program (v 3.5.2). The maximum number of joinpoints used was 4. The annual percentage change (APC %) for the final selected joinpoint model for each cohort is shown in the table. Results: The annual age-adjusted CML incidence rates for 1973 vs. 2008 were 0.72/0.67, 5.67/4.47, 0.93/0.67, and 10.5/8.5 per 100,000 population for the 4 cohorts: women (<60yr, >60yr) and men (<60yr, >60yr), respectively. Among Caucasian women (>60yr), the incidence rate decreased significantly from 5.58/100,000 in 2001 to 4.47/100,000 in 2008 (APC= -3.08, CI -5.8 to -0.3, p = 0.004). The incidence trend from 1973-2001 was stable for this cohort (APC=0.1, CI -0.3 to 0.5). The incidence trends among women <60yr, men <60yr, and men >60yr were stable from 1973-2008. Conclusions: The annual age-adjusted incidence rates of chronic myeloid leukemia among older (>60 year) Caucasian women has declined sharply from 2001-2008. The rate change is unexplained. It may help generate hypotheses regarding risk factors for CML. [Table: see text]

Event-Free Survival According to Age in Patients with Chronic Myeloid Leukemia Receiving Imatinib Frontline: The Younger, the Later, the Worse?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4038-4038 ◽  
Author(s):  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Ida Carmosino ◽  
Federico Vozella ◽  
Federico De Angelis ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Age At Diagnosis ◽  
Molecular Response ◽  
Event Free Survival ◽  
Secondary Resistance ◽  
Free Survival

Abstract Differences in baseline features and follow-up among patients with chronic myeloid leukemia (CML) according to age at diagnosis have been recently reported in cohorts from clinical controlled trials (Castagnetti F et al, 2015). To evaluate this issue in a real-life setting, we revised 207 consecutive CML patients treated at our Institution with imatinib frontline from 6/2002 to 6/2013, dividing them in young adults (>20 <45 years) (YA), middle-aged adults (≥45 <65 years) (MA) and elderly (≥65 years) (EL). The main features at baseline of the whole cohort and of the 3 age groups are reported in the Table. Table.ALLYAMAELpN° of patients207617274M/F108/8930/3140/3238/360.752Median WBC (x 109/l)IQR66.1 (32.7 - 119.0)109.8 (65.9 - 148.0)59.5 (31.3 - 126.6)40.1 (26.5 - 81.4)<0.001Median Hb (g/dl)(IQR)12.5 (11.0 - 13.5)11.7 (9.8 - 12.7)12.7 (11.0 - 14.2)12.8 (11.3 - 13.7)0.002Median PLT (x 109/l)IQR414 (275 - 616)445 (291 - 597)378 (262 - 546)457 (271 - 732)0.287Spleen enlargement (>5cm) N° (%)17 (8.3)11 (18.3)4 (5.6)2 (2.7)0.003Sokal score (N°)Low/Int/High89/93/2047/9/338/27/54/57/12<0.001Comorbidities ≥ 2, N° (%)77 (37.2)5 (8.1)26 (36.1)46 (62.1)<0.001 The rates of complete cytogenetic response (CCyR) were similar (86.4% in YA, 95.5% in MA and 91.0% in EL, p=0.227) while the rate of major molecular response was higher in the MA group (89.7% vs 63.8% in YA and 75.8% in EL, p=0.001). The number of events (permanent discontinuation due to toxicity, primary or secondary resistance, any death for CML related or unrelated causes) was lower in the MA group [8 (11.1%) vs 21 (34.4%) in YA and 28 (37.8%) in EL, p=0.001]: no difference was observed in the rate of evolution to blastic phase [3 (4.9%) in YA, 1 (1.4%) in MA and 2 (2.7%) in EL, p=0.478]. The number of deaths was higher in the EL group [12 (16.2%) vs 2 (3.2%) in YA and 0 in MA, p<0.001]: it is worth of note, however, that 11/12 deaths in the EL group were not related to CML progression. The 4-year event-free survival (EFS) for the whole cohort was 73.5% (95%CI 67.0 - 80.0): the 4-year EFS in the MA group [92.0% (95%CI 85.1 - 98.9)] was significantly higher than in YA group [67.3% (95%CI 55.1 - 79.5)] and in EL group [61.1% (95%CI 49.5 - 73.7)] (p=0.001). The 4-year overall survival (OS) for the whole cohort was 94.4% (95%CI 90.9 - 97.9): the 4-year OS in the EL group [72.4.% (95%CI 56.9 - 87.9)] was significantly lower than in YA group [96.3% (95%CI 91.2 - 100)] and in MA group (100%) (p<0.001). In conclusion, age at diagnosis influences significantly the course of CML patients treated with imatinib: the MA group has the best follow-up with an excellent OS and EFS, while the relatively lower OS and EFS in the EL group are clearly related to the incidence of unrelated deaths like in the general aged population. A possible explanation of the counterintuitive worse course of YA group is the delayed diagnosis in these patients (higher WBC counts, lower Hb levels, higher rate of spleen enlargement > 5 cm) compared to aged patients, who have often concomitant diseases and make routinely blood analyses: however, a more aggressive biology of CML in YA could not be excluded and warrants further investigations. Disclosures No relevant conflicts of interest to declare.

Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party

Blood ◽  
2011 ◽  
Vol 117 (21) ◽  
pp. 5591-5599 ◽  
Author(s):  
Gabriele Gugliotta ◽  
Fausto Castagnetti ◽  
Francesca Palandri ◽  
Massimo Breccia ◽  
Tamara Intermesoli ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Age Groups ◽  
Chronic Phase ◽  
Working Party ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Long Term Outcome ◽  
Free Survival

AbstractThe median age of chronic myeloid leukemia (CML) patients is ∼ 60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship between age and outcome in 559 early chronic-phase CML patients enrolled in 3 prospective clinical trials of Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party, treated frontline with IM, with a median follow-up of 60 months. There were 115 older patients (≥ 65 years; 21%). The complete cytogenetic and major molecular response rates were similar in the 2 age groups. In older patients, event-free survival (55% vs 67%), failure-free survival (78% vs 92%), progression-free survival (62% vs 78%), and overall survival (75% vs 89%) were significantly inferior (all P < .01) because of a higher proportion of deaths that occurred in complete hematologic response, therefore unrelated to CML progression (15% vs 3%, P < .0001). The outcome was similar once those deaths were censored. These data show that response to IM was not affected by age and that the mortality rate linked to CML is similar in both age groups. This trial was registered at www.clinicaltrials.gov as #NCT00514488 and #NCT00510926.

scholarly journals Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6269
Author(s):  
Michael Daskalakis ◽  
Anita Feller ◽  
Jasmine Noetzli ◽  
Nicolas Bonadies ◽  
Volker Arndt ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Age Groups ◽  
Cancer Registries ◽  
Population Based ◽  
Older Age ◽  
Similar Data ◽  
Real World Data

Background: Tyrosine kinase inhibitors (TKI) substantially improved chronic myeloid leukemia (CML) prognosis. We aimed to describe time period- and age-dependent outcomes by reporting real-world data of CML patients from Switzerland. Methods: Population-based incidence, mortality, and survival were assessed for four different study periods and age groups on the basis of aggregated data from Swiss Cantonal Cancer Registries. Results: A total of 1552 new CML cases were reported from 1995 to 2017. The age-standardized rate (ASR) for the incidence remained stable, while the ASR for mortality decreased by 50–80%, resulting in a five-year RS from 36% to 74% over all four age groups. Importantly, for patients <60 years (yrs), the five-year RS increased only in earlier time periods up to 92%, whereas for older patients (+80 yrs), the five-year RS continued to increase later, however, reaching only 53% until 2017. Conclusions: This is the first population-based study of CML patients in Switzerland confirming similar data compared to other population-based registries in Europe. The RS increased significantly in all age groups over the last decades after the establishment of TKI therapy. Interestingly, we found a more prominent increase in RS of patients with older age at later observation periods (45%) compared to patients at younger age (10%), implicating a greater benefit from TKI treatment for elderly occurring with delay since the establishment of TKI therapy. Our findings suggest more potential to improve CML therapy, especially for older patients.

scholarly journals Characteristics, Treatment and Outcome of 15 to 18 Years-Old Adolescents with Chronic Myeloid Leukemia (CML): The Experience of the International Registry of Childhood CML (I-CML-Ped Study)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3602-3602
Author(s):  
Morgane Froment ◽  
Meinolf Suttorp ◽  
Stéphanie Ragot ◽  
Hélène Deutsch ◽  
Violaine Goyeau ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Age At Diagnosis ◽  
Response To Treatment ◽  
Costal Margin ◽  
First Line ◽  
Hematopoietic Stem ◽  
International Registry

Abstract Introduction: CML is a rare disease in children and adolescents, accounting for 2-3% of leukemia cases in this population. Pediatric CML is more frequent in the 2 nd decade of life but data on adolescents are limited. Only response to treatment has been analyzed in few studies and seems to be poorer in this age cohort. The International Registry of Childhood Chronic Myeloid Leukemia gave us the opportunity to analyze the characteristics and outcome in a large cohort of adolescents. Aims and objectives: To report on clinical features and response to treatment in adolescents (15-18 years of age at diagnosis) with CML in chronic phase (CML-CP). Material and methods: The International Registry of Childhood CML (I-CML-Ped Study, registered at www.clinicaltrials.gov NCT01281735) enrolled patients less than 18 years of age at diagnosis of CML in all phases according to the criteria of the European Leukemia Net (ELN). Data from this registry collected from Jan 2011 - Mar 2021 into the I-CML-Ped Study (Poitiers, France) were retrospectively analyzed. Results: Out of 614 patients (pts) registered in the I-CML-Ped Study, we identified 144 (23.4%) adolescents (15-18 years of age at diagnosis) with sufficient available data. Among them, according to the ELN criteria, 132 (92%), 7 (5%), and 5 (3%) pts presented with CML-CP, accelerated phase (AP), and blastic phase (BP), respectively. The median age of the cohort comprising 132 adolescents with CML-CP was 16.2 years [range, 15-18]. Ratio male/female was 1.75. Splenomegaly was reported in 66% of the pts with a median spleen size of 11.5 cm below the costal margin [range, 1-32]. Hepatomegaly was reported in 31% of the pts with a median liver size of 2.5 cm below the costal margin [range, 1-19]. Pain, asthenia and weight loss were the most frequent symptoms at diagnosis in 35%, 33%, and 20% of pts, respectively. The performance status according to the OMS and Karnofsky scores were 0 and 100% in 81% and 57% of the pts, respectively. At diagnosis, median leukocyte count was 181 G/L [range, 7-820]; median platelet count was 516 G/L [range, 102-2619], and median hemoglobin level was 10.45 g/dL [range, 4-17]. BCR-ABL1 transcript type b3a2 was present in 53% of the assessable pts. Additional chromosomal abnormalities and variants were found in 5% of the pts. 9% and 40% of pts were considered at high-risk according to the ELTS score and to the Sokal score (for pts less than 45 years), respectively. The majority of pts (97%) were treated with imatinib as first line treatment. After 12 months of treatment, in pts with data available, rate of complete cytogenetic response (CCyR) was 74/109 (68%) pts with imatinib first line. Overall, rate of CCyR was 101/109 (93%) pts with imatinib first line [88/109 (81%) pts receiving imatinib only, 13/109 (12%) pts after switching to another TKI, 8/109 (7%) pts did not achieve CCyR]. Median time to achieve CCyR was 8.2 months [range, 2.7-106.7]. The cumulative rate of MMR at month 12 was 40/111 (36%) pts. Overall rate of MMR was 91/111 (82%) pts [72/111 (65%) pts with first line imatinib only; 19/111 (17%) pts with another TKI]. Median time to achieve first MMR was 14.5 months [range, 0.9-63.1]. Out of all patients on first line imatinib, 11/123 (9%) pts progressed: 3/11 pts progressed to AP and 8/11 pts to BP. Further progress to BP was observed in 2 of the 3 pts with AP. BP phenotype was myeloid in 5/10 pts, lymphoid in 3/10 pts and bilineage in 1/10 pts (no data for 1/10 pts). With imatinib first line, deaths occurred in 5/123 (4%) pts, among them 4/5 due to complications associated with hematopoietic stem cell transplantation. With a median follow up of 37 months [range, 0.9-231], the overall survival rate was 89.2% [83.6%; 94.7%] for pts treated with imatinib first line (N = 123). Conclusion: Our results are in line with publications describing adolescents and young adults (AYAs) as a risk population for a poorer treatment outcome: when comparing AYAs (15-29 yrs) to adults (&gt;30 yrs), CCyR and MMR were inferior in AYAs (cumulative CCyR 84% vs 93%, cumulative MMR 75% vs 86%, respectively) [Pemmaraju N et al., Haematologica 2012] and rates of progression to AP and BP were 8.7% in AYAs (16-29 yrs) but only 5.3% and 6.1% in adults (45-59 yrs and &gt;60 yrs, respectively) [Kalmanti L et al. , Ann Hematol. 2013]. Additional research is required in adolescents with CML to shed light on the cause(s) for the observed differences and to further improve the outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Exploring Disease Biology in Hispanic Versus Non-Hispanic Patients with Diffuse Large B-Cell Lymphoma (DLBCL) to Explain Survival Disparities

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4867-4867
Author(s):  
Sikander Ailawadhi ◽  
Alvaro J. Alencar ◽  
Madiha Iqbal ◽  
Prachi Jani ◽  
Salman Ahmed ◽  
...  
Keyword(s):  
Ethnic Minorities ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Age At Diagnosis ◽  
Stage Iii ◽  
Disease Stage ◽  
Ki 67 ◽  
Patient Level ◽  
Significant Difference ◽  
Hispanic Patients

Abstract Background: DLBCL is the most common adult NHL and despite significant advancements, outcomes in ethnic minorities remain suboptimal. Factors responsible for these disparities in ethnic minorities, especially variability in clinical and pathological features with evaluation of patient-level data have not been studied. Methods: A multi-institutional database of DLBCL patients seen at Mayo Clinic in Florida, University of Miami and University of Southern California between 1996-2016 was developed. Patient demographics, clinical disease characteristics and details of DLBCL immunophenotype [CD10, MUM1, BCL6 (Han's classification), Ki 67, MYC, BCL2) were reviewed. Comparisons between Hispanic and Non-Hispanic patients were made by Chi-square, Fischer's exact and Signed rank tests, where applicable. Patients with missing data on a certain feature were not included in the statistical analysis of that specific characteristic. Results: A total of 966 DLBCL patients with 69 Hispanics and 752 non-Hispanics were identified. These included 52% males (N=36) and 48% females (N=33) in Hispanics versus 58% males (N=436) and 42% females (N=316) in Non-Hispanics (p=0.35). Median age at diagnosis was significantly lower at 61 years (range 27-89) in Hispanics versus 66 in non-Hispanics (p=0.014). Extranodal disease was seen significantly more commonly in Hispanics (74%) than in non-Hispanics (60%) (p=0.037). There was no significant difference in disease stage at presentation between the two cohorts (p=0.189) although the proportion of patients with stage III and IV disease was higher among Hispanics (80.4%) as compared to non-Hispanics (68.5%). Similarly there was no significant difference in presence of primary CNS DLBCL at diagnosis between the two groups (p=0.74). GCB phenotype per the Hans' classification was seen in 59% (N=29) in both, Hispanics and Non-Hispanics (N=241) (p=0.99). Similarly, the median ki67 index of 80% was seen in both cohorts (p=0.48). MYC was positive in 59% in Hispanics versus only 37.5% in non-Hispanics (p=0.024). BCL2 expression by itself and also combined BCL2 and MYC double expression were not significantly different between the two groups (p=0.58 and p=0.11, respectively). Median overall survival (OS) was 22.5 months in Hispanics compared 54.9 months in Non-Hispanics (p<0.0001) (Figure 1). Conclusion: Survival outcome disparities in racial and ethnic minorities have been previously reported from population-based analyses. Lack of patient-level clinical data makes these analyses hypothesis generating, but not conclusive. We confirmed some prior findings including younger age at diagnosis for Hispanics with DLBCL. We also reported greater incidence of extranodal as well as stage III or IV disease at the time of presentation among Hispanics which may contribute to poor outcomes in this population. From DLBCL pathology standpoint, we found increased expression of MYC among Hispanics but no other significant immunohistochemical differences including double expression or non-GCB phenotype. The inferior OS despite uniform treatment practices at large Cancer Centers suggest multifactorial influences on patient outcomes which may at least in part include some of the differences we report here. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document