Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials

Abstract

© F e r r a t a S t o r t i F o u n d a t i o nthis on-site documentation, causes of death were grouped into the following categories: therapy-related, CLL-related, CLL-unrelated, or unknown. Both studies were approved by the Institutional Review Board and Ethics Committee of the University of Munich and performed in accordance with the Declaration of Helsinki. Comorbidity assessmentFor both trials, comorbid conditions present at baseline had to be assessed and documented in the patient's case report form by the treating physician. Further quantification of the comorbidity burden by use of specific comorbidity scores was not part of the study protocols. Thus, all comorbid conditions reported within the case report form were captured only in a qualitative manner. Health problems resulting from the CLL itself and CLL as the primary disease were not recorded as comorbidity.To assess the comorbidity burden for each patient individually in the absence of quantitative data derived from scores, the number of comorbidities was calculated as the sum of all conditions abstracted from the patient's case report form according to the rules described above. Since information on the severity of comorbid conditions was mostly unobtainable, a retrospective scoring of comorbidity by use of a validated comorbidity score was not reliably possible (although an attempt was made to calculate the Charlson comorbidity index from the available data). 16 For a general description of the spectrum of comorbidities in the study population, each of the concomitant diseases was assigned to disease categories abstracted from the Cumulative Illness Rating Scale. 17 Statistical analysisThe statistical analysis was performed with SPSS 17 software (SPSS Inc., USA) and based on data collected by Results Baseline characteristicsOf the 581 patients recruited into the CLL4 and CLL5 trials, 555 were eligible for this analysis. Twenty-six patients were excluded because of inaccurate diagnosis (n=5), no need of therapy (n=2), previous therapy (n=3), consent issues (n=6), or other reasons (n=10). The characteristics of the study population are summarized in Table 1. The median time of follow-up for all patients was 58 months. Patients treated within the CLL4 and CLL5 trials were younger and older, respectively (median: 58 versus 70 years). Comorbidity burdenThe patients' comorbidity burden at baseline is presented in Table 2 and Online Supplementary Table S1. Fifty-three percent of the patients had at least one concurrent disease. The number of comorbidities ranged from zero to seven (median: 1) and increased continuously with advanced age (P<0.001). Of 139 patients presenting with more than one comorbidity, most had two or three co-existing diseases, while there were only 24 patients with more than three health problems. Impact of comorbidity on overall prognosisBy univariate analysis, patients with ≥2 comorbidities had a significantly shorter median overall survival than patients with <2 comorbid conditions (71.7 versus 90.2 months, P<0.001). ...

Chronic lymphocytic leukemia in the elderly: clinico-biological features, outcomes, and proposal of a prognostic model

“…13 However, we detected a relationship between overall response rate and comorbidity at time of treatment (CIRS-T), which is in line with other studies. 18,19 A moderate to severe comorbidity burden (CIRS-D >6 and CIRS-T >4) was strongly associated with shorter overall survival. Of note, the cutoff that better correlated with overall survival (CIRS-T >4) was different from that in other studies.…”

“…[17][18][19] In a pooled analysis comprising 555 patients comorbidity had an independent impact on overall survival (71.7 versus 90.2 months; P<0.001) due to higher therapy-related, CLL-unrelated, and, particularly, CLL-related deaths. 19 In the present study we assessed comorbidity by CIRS 12,13 at diagnosis (CIRS-D) and prior to first treatment (CIRS-T). No correlation was found between comorbidity and performance status, which is in agreement with other studies.…”

Renal insufficiency is an independent prognostic factor in patients with chronic lymphocytic leukemia

“…Several studies have found an association between comorbidities and survival in CLL, although renal function was either not included or not analyzed individually in these reports. 8,9 Our data reveal that RI appears to have an independent prognostic role in patients with CLL. Given this, we would propose that the impact of RI as a prognostic comorbid feature warrants validation in prospective studies, along with other previously recognized comorbidities.…”

Aging and malignant hemopathies

“…Looking at the different items in terms of number and severity, it appeared that 5-year mortality was 40% for patients with more than 2 co-morbidities, compared to 25% for those with less than 2 co-morbidities. 19 Among the various scales of the CGA, a co-morbidity index (CIRS) has been correlated with overall survival and is currently used as a decision tool for inclusion in German CLL trials. Data from the CLL8 trial (n=817), where patients were randomized between FCR and FC and where CIRS was mandatory (exclusion if CIRS >6), showed that a CIRS Editorials score over 3 in this selected population was a prognostic factor correlated with OS independent of age, ECOG status and other CLL prognostic factors.…”