scholarly journals CD49d Is the Strongest Flow Cytometry–Based Predictor of Overall Survival in Chronic Lymphocytic Leukemia

2014 ◽  
Vol 32 (9) ◽  
pp. 897-904 ◽  
Author(s):  
Pietro Bulian ◽  
Tait D. Shanafelt ◽  
Chris Fegan ◽  
Antonella Zucchetto ◽  
Lilla Cro ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Cox Model ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Bivariate Analysis ◽  
Prognostic Information ◽  
Early Stage Disease ◽  
The Impact

Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry–based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry–based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. Conclusion In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry–based predictor of OS and TFS in CLL.

scholarly journals CD49d Is The Strongest Flow Cytometry-Based Predictor Of Overall Survival In Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 672-672 ◽  
Author(s):  
Pietro Bulian ◽  
Tait D Shanafelt ◽  
Chris Fegan ◽  
Antonella Zucchetto ◽  
Lilla Cro ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Research Funding ◽  
Early Stage ◽  
Cox Model ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Bivariate Analysis ◽  
The Impact

Abstract Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multi-center analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as overall survival (OS) and treatment free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cut-off. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLL, and Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry-based prognosticators (CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥30% of neoplastic cells expressing CD49d were considered CD49d+. The decrease in OS at 5 and 10-years among CD49d+ cases was 7% and 23% (decrease in TFS 26% and 25% respectively). The pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR=2.0) in a Cox model adjusted for clinical and biological prognosticators. Hierarchical trees including all cases, or restricted to early stage or patients ≤65 years, always selected CD49d as the most important flow-cytometry-based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patients' subsets with poorer outcome independent of CD38 and ZAP-70. Conclusions In this analysis of ∼3000 patients, CD49d emerged as the strongest flow cytometry-based predictor of OS and TFS in CLL. Disclosures: Shanafelt: Genentech: Research Funding; Glaxo-Smith-Kline: Research Funding; Cephalon: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Polyphenon E International: Research Funding. Burger:Pharmacyclics: Research Funding.

scholarly journals COVID-19 Vaccine Failure in Chronic Lymphocytic Leukemia and Monoclonal B-Lymphocytosis; Humoral and Cellular Immunity

2021 ◽  
Author(s):  
Yanodng Shen ◽  
Jane A Freeman ◽  
Juliette Holland ◽  
Ann Solterbeck ◽  
Kartik Naidu ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Spike Protein ◽  
Post Dose ◽  
Early Stage Disease ◽  
Humoral And Cellular Immunity ◽  
Protein Levels ◽  
Treatment Naïve

Chronic lymphocytic leukemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-Lymphocytosis (MBL) patients also have immune impairment. We evaluated humoral and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion (<50AU/mL SARS-CoV-2 II IgG assay, antibody to spike protein, Abbott Diagnostics) following each of 2 vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL respectively remained seronegative, indicating 2 vaccine doses are crucial. There was significant association between post-dose 2 antibody level with pre-vaccination reduced IgM (p<0.0001), IgG2 (p<0.035), IgG3 (p<0.046), and CLL therapy within 12 months (p<0.001) in univariate analysis. By multivariate analysis, reduced IgM (p<0.0002) and active therapy (p<0.0002) retained significance. There was no significant correlation with age, gender, CLL duration, IgG, IgA or lymphocyte subsets. Anti-spike protein levels varied widely and were lower in CLL, than MBL, and both lower than normal donors. Neutralization activity showed anti-spike levels <1000AU/mL were usually negative for both an early viral clade and the contemporary Delta variant. There were 72.9% of CLL and 53.3% of MBL who failed to reach anti-spike levels >1000AU/mL. In a representative subset of 32 CLL patients, 80% had normal T-cell responses by IFNγ and IL-2 FluoroSpot assay. Failed seroconversion occurred in 36.6%% of treatment-naive patients, 52.9% treatment-naive with reduced IgM, 78.1% on therapy, and 85.7% on ibrutinib. Vaccination failure is very common in CLL, including early-stage disease.

Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4679-4685 ◽  
Author(s):  
William G. Wierda ◽  
Susan O'Brien ◽  
Xuemei Wang ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Model ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Early Stage Disease ◽  
Staging Systems

Abstract The clinical course for patients with chronic lymphocytic leukemia is extremely heterogeneous. The Rai and Binet staging systems have been used to risk-stratify patients; most patients present with early-stage disease. We evaluated a group of previously untreated patients with chronic lymphocytic leukemia (CLL) at initial presentation to University of Texas M. D. Anderson Cancer Center to identify independent characteristics that predict for overall survival. Clinical and routine laboratory characteristics for 1674 previously untreated patients who presented for evaluation of CLL from 1981 to 2004 were included. Univariate and multivariate analyses identified several patient characteristics at presentation that predicted for overall survival in previously untreated patients with CLL. A multivariate Cox proportional hazards model was developed, including the following independent characteristics: age, β-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups. Inclusion of patients from a single institution and the proportion of patients younger than 65 years may limit this model. A weighted prognostic model, or nomogram, predictive for overall survival was constructed using these 6 characteristics for 5- and 10-year survival probability and estimated median survival time. This prognostic model may help patients and clinicians in clinical decision making as well as in clinical research and clinical trial design.

Management of Chronic Lymphocytic Leukemia

2015 ◽  
pp. 164-175 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Richard R. Furman ◽  
Clive S. Zent
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Signaling Pathway ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Management Approach ◽  
Team Approach ◽  
Early Stage Disease ◽  
Asymptomatic Patients ◽  
Wide Range ◽  
Bcr Signaling

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for “active disease,” which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/ TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

Early Ofatumumab Treatment For High-Risk, Treatment-Naive Patients With Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5307-5307
Author(s):  
Nitin Jain ◽  
Michael J. Keating ◽  
Alessandra Ferrajoli ◽  
Marina Konopleva ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Delay Time ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Tumor Lysis ◽  
Ighv Gene ◽  
Grade 3

Background Ofatumumab is a human IgG1-kappa monoclonal antibody that binds to CD20 on normal B cells and on B chronic lymphocytic leukemia cells, resulting in B cell lysis. Ofatumumab has single-agent activity in patients (pts) with refractory CLL (Wierda, JCO 2010). Pts with CLL who have early stage disease (Rai 0-II) but have high-risk prognostic markers such as deletion 17p or deletion 11q have an increased risk of disease progression. Currently, these pts are offered watch-and-wait approach. The objective of this Phase II study is to evaluate the efficacy of ofatumumab in treating these pts with the goal to delay time to first chemoimmunotherapy treatment. Methods Pts with CLL/SLL were eligible provided they had high-risk for progression based on the presence of at least one of the following features: Rai stage II, serum beta-2 microglobulin (β2M) ≥3 mg/L, absolute lymphocyte count ≥25,000/µL, unmutated (≤2%) IGHV gene or mutated IGHV3-21, ZAP70 positive, CD38 positive (≥ 30%), or 11q or 17p deletion by FISH. Pts having a 2008 IWCLL/NCI-WG indication for CLL treatment were not eligible. Pts with Rai stage III-IV CLL were not eligible. Ofatumumab 300 mg dose 1, then 1000 mg weekly for 7 additional weeks (8 doses) was administered. Response assessment, including bone marrow evaluation, was done at least 2 months after last dose of ofatumumab and pts were followed for progression-free survival and time to first chemoimmunotherapy. Results Twenty-five pts (9 women, 16 men) were enrolled so far. The median age was 59 yrs (range, 40-81). The baseline characteristics are listed in the Table. Fifty percent of pts had unmutated IGHV gene. Thirty-four percent of pts had high-risk cytogenetic by FISH analysis. The median follow-up on the study is 4.7 months (range, 0.5-26). Grade 3-4 adverse events included infusion reaction in 6 pts. Autoimmune hepatitis with grade 4 ALT, grade 4 AST, and grade 4 alkaline phosphatase elevations was seen in 1 pt. Other grade 3-4 toxicities included rash (1 pt), shingles (1 pt), and tumor lysis (1 pt). Tumor lysis was seen in the pt with the WBC count of 207 K/µL. Eighteen pts (7 too early) are evaluable for response. Responses are as follows: 6 CR, 3 nPR, 3 PR, and 6 with stable disease. Three pts have progressed at 18.8, 14.1 and 3.2 months after starting the study treatment; 2 pts had unmutated IGHV gene (FISH negative) and one pt had trisomy 12 (IGHV mutation status unknown). None of the pts with deletion 17p or deletion 11q have progressed. All pts are alive at this time. The median overall follow up time is 7.6 months (range, 1-28). Conclusions Ofatumumab is well tolerated in pts with early stage CLL and may delay time to first chemoimmunotherapy. Disclosures: Ferrajoli: GlaxoSmithKline: Research Funding.

Chronic Lymphocytic Leukemia

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 193-213 ◽  
Author(s):  
Neil E. Kay ◽  
Terry J. Hamblin ◽  
Diane F. Jelinek ◽  
Gordon W. Dewald ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Disease Progression ◽  
Early Stage ◽  
Diagnostic Procedures ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Prognostic Features ◽  
Stage Disease

Abstract This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management. In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early “preclinical” phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease. In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered. In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.

Flow Cytometric Detection of ZAP-70 in Chronic Lymphocytic Leukemia: Correlation With Immunocytochemistry and Western Blot Analysis

2007 ◽  
Vol 131 (1) ◽  
pp. 50-56
Author(s):  
Graham W. Slack ◽  
Juanita Wizniak ◽  
Laith Dabbagh ◽  
Xinzhe Shi ◽  
Pascal Gelebart ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Specimen Processing

Abstract Context.—Expression of ZAP-70 in chronic lymphocytic leukemia (CLL) predicts worse clinical outcome in patients with early-stage disease. It has become important to include ZAP-70 in the immunophenotyping panel used to diagnose CLL, commonly performed by flow cytometry (FC). Nevertheless, the methodology used to detect ZAP-70 by FC has not been extensively evaluated. Objective.—To describe our FC method for detecting ZAP-70 in CLL and assess whether this assay is useful in estimating the ZAP-70 protein level in CLL cells. Design.—ZAP-70 expression was assessed by FC in 45 consecutive newly diagnosed CLL patients, and the results were correlated with those of immunocytochemistry and Western blot analysis. Results.—With &gt;25% ZAP-70–positive B cells as the cutoff, the FC results had a perfect concordance with those of immunocytochemistry (39/39, 100%) and Western blot analysis (7/7, 100%). The use of autofluorescence controls was found to be superior to other alternatives. Overall, 19 (42%) of 45 cases were ZAP-70 positive in our series. Since only 7 cases (16%) had &gt;20% to 30% ZAP-70–positive B cells, the cutoff of &gt;25% readily separated CLL into positive and negative groups in most cases. ZAP-70 positivity was significantly associated with atypical morphology but not other laboratory parameters evaluated. Conclusions.—With proper specimen processing and the use of directly fluorescence-conjugated anti–ZAP-70 antibody, one can readily incorporate ZAP-70 into the routine FC study panel for CLL. Our data suggest that FC is a rapid and useful method to estimate the ZAP-70 protein expression level in CLL.

Combinations of ZAP-70, CD38 and IgVH Mutational Status as Predictors of Time to First Treatment in CLL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 711-711
Author(s):  
Alison Morilla ◽  
David Gonzalez ◽  
Ilaria Del Giudice ◽  
Ricardo Morilla ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
P Value ◽  
Prognostic Information ◽  
Free Interval ◽  
Mutational Status ◽  
Prognostic Group ◽  
Time To First Treatment ◽  
The Impact

Abstract The prognostic value of ZAP-70, CD38 expression and IgVH somatic hypermutation(SHM) in CLL has been well documented. We investigated whether the proposed model of combining ZAP-70 and CD38 levels to identify patients likely to progress (Del Giudice et al 2005, Schroers et al 2005) remained valid when mutational status was considered and studied which combinations of these 3 parameters provided the most valuable prognostic information. ZAP-70 and CD38 were evaluated by flow cytometry and IgVH SHM was analysed by direct sequencing with 98% cut off. All 3 parameters were studied in 115 untreated CLL patients, 90% of which were advanced stage:(stage A stable 10%, stage A progressive 30%, stage B 37%, and stage C 23%). ZAP-70 and IgVH SHM showed 68% concordance, CD38 and IgVH SHM concordance of 69% and 75% of patients, using cut offs of ≥30% and ≥7%, respectively. The impact on time to first treatment /treatment free interval (TFI) for these parameters can be seen in Table 1. Treatment Free Interval (TFI )and Prognostic Factors No.of Cases Median TFI (months) P Value TFI=Time from diagnosis to date of first treatment Mutational status Umutated 68 23 0.00003 Mutated 47 61 ZAP70 ≥20% Positive 37 24 0.00055 Negative 78 44 CD38 ≥7% Positive 79 25 0.0005 Negative 36 61 Mutation/ZAP70 ZAP70+/Unmutated 35 19 0.002 Discordants 36 25 ZAP70-/Mutated 44 64 Mutation/CD38 ≥7% CD38+/unmutated 59 21 0.004 Discordants 29 37 CD38-/Mutated 27 77 ZAP70/CD38 ≥7% ZAP70+/CD38+ 34 19 0.003 Discordants 48 39 ZAP70-/CD38- 33 72 Mutation/ZAP70/CD38 ≥7% ZAP70+/CD38+/Unmutated 32 20 0.007 Discordants 57 30 ZAP70-/CD38-/Mutated 26 75 Univariate analysis showed significance for TFI, for each variable. Regardless of the combinations used, 2 or all 3 variables provided significant prognostic information with respect to TFI. An intermediate prognostic group was identified for discordant cases. CD38 ≥7% proved a more significant value than ≥30% for this series, hence this cut off was used for subsequent analysis. IgVH SHM/CD38 provided the best discrimination between favourable and unfavourable prognostic groups, in relation to TFI, with the least number of discordants. Concordant cases of CD38+/ZAP70+ were able to positively predict unmutated status in 94.1% of cases and ZAP70-/CD38- cases predicted mutated status in 78.8% of patients. The discordant ZAP70/CD38 cases could be further stratified by testing IgVH SHM (mutated cases median TFI: 42 m, unmutated cases median TFI: 19 m). Amongst the cases discordant for ZAP/CD38/IgVH SHM, the largest group (40%), was ZAP70 -/CD38+ /unmutated and showed median TFI:25m, comparable to the worst prognostic group for all combinations. There was no evidence of preferential IgVH gene usage in this discordant group. In conclusion we have shown that combining IgVH SHM/CD38 provides more refined prediction of TFI in this group. Combination of ZAP-70 and CD38 is useful for predicting time to first treatment without the need for IgVH SHM analysis, in concordant cases. Thus these simple tests( ZAP-70 and CD38), performed by flow cytometry continue to provide relevant prognostic information,although IgVH SHM is still the paradigm.

Impact of immunoglobulin heavy chain variable region mutational status on the outcome of patients with chronic lymphocytic leukemia harboring isolated 13q deletion.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6608-6608
Author(s):  
Gelenis C. Domingo ◽  
Samir Dalia ◽  
Julio C. Chavez ◽  
Estrella M. Carballido ◽  
Paibel I. Aguayo-Hiraldo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Demographic Data ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Prognostic Information ◽  
Cytogenetic Abnormalities ◽  
Mutational Status ◽  
The Impact ◽  
13Q Deletion

6608 Background: Several prognostic factors can predict the course of chronic lymphocytic leukemia (CLL). Among them, the IGVH mutational status and the presence of cytogenetic abnormalities are the strongest predictors of outcome. Mutated IGVH and deletion 13q independently confer a survival advantage. CLL patients with mutated IGVH in combination with deletion 13q have a better prognosis when compared to their unmutated IGVH counterparts. However, there is limited data on the outcome of patients harboring favorable deletion 13q and the unfavorable unmutated IGVH. This study aimed at identifying patients with these two indicators in order to obtain important prognostic information. Methods: We used the Moffitt Cancer Center Total Cancer Care (TCC) database to find patients with a diagnosis of CLL between January 1993 and December 2009. Individual charts were reviewed for demographic data and CLL cytogenetics, including IGVH mutation status and presence of deletion 13q. We analyzed the impact of having deletion 13q in combination with an unmutated IGVH on the overall survival (OS) for this subset of CLL patients using Kaplan Meier curves with SPSS statistical software. Results: 546 patients were identified during the aforementioned time period with a diagnosis of CLL. Median age was 62.5 years. 144 (26.4%) of these patients had IGVH and cytogenetic analysis available. 53 patients had 13q deletion as their sole genetic abnormality. Patients with unmutated IGVH and positive for deletion 13q were 19/53 (35.8%). Patients with mutated IGVH and positive for deletion 13q were 34/53 (64.2%). Patients with mutated IGVH and positive for deletion 13q had an OS of 17 years. While patients with unmutated IGVH and positive deletion 13q had a lower median OS of 12 years (91.2% vs 78.9%, p=0.05). Hazard ratio for patients with IGVH mutated and positive deletion 13q was 0.4, p=0.05. Conclusions: Mutated IGVH appears to be associated with improved OS in patients with isolated 13q deletion when compared to patients with unmutated IGVH and isolated 13q deletion. Further research is needed to assess these mutations in relation to other cytogenetic abnormalities in CLL.

scholarly journals Leukemia Cutis As an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5461-5461
Author(s):  
Mahmood B Aldapt ◽  
Mohamed A Yassin
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Skin Lesions ◽  
Lymphocytic Leukemia ◽  
Treatment Modalities ◽  
Skin Involvement ◽  
Skin Infiltration ◽  
Leukemia Cutis ◽  
Cutaneous Response ◽  
The Impact

Introduction Cutaneous infiltration (Leukemia cutis) by CLL is regarded as specific sign of skin involvement, these findings can vary in presentations; they can be localized or generalized in the form of erythematous papules, plaques, nodules, and large tumors, however ulceration is uncommon. Skin lesions in general can be seen in 25% of patients with CLL. It is unclear what is the impact of cutaneous infiltration by CLL on prognosis, mainly because most cases are sporadic, either in case reports or series, with no consistency in the modality of treatment. Patients and methods A systematic search of the Medline database (PubMed), Google Scholar was performed to identify English language articles published from Jan 2000 to June 2019 with the following search terms: Leukemia cutis - CLL, cutaneous - CLL, skin - CLL, cutaneous - chronic lymphocytic leukemia, skin - chronic lymphocytic leukemia. Only patients with confirmed CLL Leukemia cutis were included in this analysis. Results A total of 56 cases were identified, with median age of 66 years (range from 39-90), of these cases 43 (76.8%) were males and 12 (21.4%) were females, with ratio of 3.6 : 1. Head and neck were the most common involved sites, interestingly it was very common on the earlobes, followed by trunk and extremities. The most common clinical presentation was papulonodular skin lesions, others like erythematous patches were seen, but ulceration was uncommon. Most cases had leukemia cutis as the initial presentation of CLL. The median time before relapse with skin involvement was 5.5 years (range 1 to 21 years). Most patients were diagnosed at early stage. Majority were treated with chemotherapy, others managed by observation, local radiotherapy or chemoimmunotherapy. In general, 35 (62.5%) cases had cutaneous response to treatment (25 CR and 10 PR). Discussion CLL skin infiltration is not uncommon, but it is not well described in the literature, here in our review we revisited specific cutaneous infiltration by CLL, we emphasized on Leukemia cutis rather than general secondary skin manifestations in CLL. Many cases had CLL skin involvement at the site of old herpetic lesions, which raises the hypothesis of monoclonal B-cells antigenic recruitment, rather than true metastasis. Most presentations came as first sign of the disease, and mostly in early stage. It was also observed that skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with very low progression rate. Because of the rarity of the disease, treatment modalities varied widely, and there was no consensus on treatment, yet all treatment modalities resulted in cutaneous response rate of 62.5%. The best modality of treatment in cutaneous CLL is based on the staging, lesions distribution (localized vs. generalized) and co-morbidities. Conclusion Leukemia cutis is rare but rather a recognized complication of CLL, most likely presents as papulonodular lesions as initial sign of the disease, furthermore most patients present in early stage, it is observed that all patients ≤60 year old had early stage disease, patients with early stage and localized leukemia cutis can benefit from observation alone strategy, on the other hand all patients with advanced stage were >60 year old, and intervention in these patients is warranted, in other situations treatment is individualized based on staging, lesions distribution (localized vs. generalized) and comorbidities. Leukemia cutis did not affect the prognosis of the disease. Disclosures No relevant conflicts of interest to declare.

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