Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in chronic lymphocytic leukemia (original) (raw)
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Mayo Clinic Proceedings, 2007
Recently developed prognostic tests in early Rai and Binet stage chronic lymphocytic leukemia (CLL) require considerable technologic expertise and are not available worldwide. Smudge cells are CLL cells ruptured during smear preparation. We hypothesized that smudge cell formation is inversely correlated with expression of vimentin, a cytoskeletal protein and prognostic marker, and that the percentage of smudge cells would predict prognosis in CLL. We reviewed the blood smears of 75 patients with previously untreated early-and intermediate-stage CLL (Rai stage 0-II) who were seen at the Mayo Clinic in Rochester, Minn, between September 1989 and December 2000. A total of 200 lymphocytes and smudge cells were counted on each slide and the results expressed as a percentage of the total lymphocytes (intact and smudged). The median percentage of smudge cells was 27% (range, 4%-72%). The percentage of smudge cells inversely correlated with vimentin expression (r=-0.57; P=.007). The median percentage of smudge cells was higher in patients with the mutated immunoglobulin heavy chain gene than in those with the unmutated immunoglobulin heavy chain gene (31% vs 13%; P=.02). Patients with less than 30% smudge cells had a median time from diagnosis to initial treatment of 72.7 months, whereas the median time from diagnosis to initial treatment in patients with 30% or more smudge cells was not reached (P=.001). The percentage of smudge cells as a continuous variable correlated with overall survival (P=.04). The estimation of smudge cells on a blood smear could be a universally available prognostic test in early-stage CLL.
Hematology, Transfusion and Cell Therapy, 2022
Objective: We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods: In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results: The mean age was 63 years (48-85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p = 0.0009), CD38 expression (p = 0.039), unmutated IGVH status (p = 0.0009) and presence of cytogenetic abnormalities (for del 13q, p = 0.0012, while for other cytogenetic aberrations, p = 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r =-0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p = 0.41) or gender (median, 19% for males vs. 20% for females; p = 0.76). Conclusion: When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.
Clinical Lymphoma Myeloma and Leukemia, 2014
We highlight, the use of smudge cell percentage on peripheral smear of chronic lymphocytic leukemia (CLL) patients at centers with limited resources. Introduction/Background: Smudge cells are ruptured lymphocytes present on routine blood smears of chronic lymphocytic leukemia (CLL) patients. We evaluated prognostic and predictive significance of smudge cell percentage on a blood smear in CLL patients. Materials and Methods: We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears of 222 untreated CLL patients registered at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi over the past 12 years. Results: The male:female ratio was 3:1, and median age 60 (range, 28-90) years. Median absolute lymphocyte count was 42 Â 10 9 /L. The median smudge cell percentage was 29.6% (range, 4%-79%). We found no correlation of proportion of smudge cells with age, sex, lymphocyte count, organomegaly, or response to therapy, although there was a significant correlation with the Rai stage at diagnosis. Median smudge cell percentage in stage 0 and I was 33% (range, 12%-79%), in stage II 31% (range, 12%-61%), and stage III and IV 21% (range, 4%-51%) (P < .001). Patients with 30% smudge cells had a shorter median progression-free period (PFP) of 30 months compared with patients who had more than 30% smudge cells (PFP, 45 months; P ¼ .01). The 5-year survival rate was 51% for patients with 30% or fewer smudge cells, and it was 81% for patients with more than 30% smudge cells (P < .001) at a median follow-up of 3.5 years. Conclusion: Simple and inexpensive detection of smudge cells on routine blood smears seems useful in predicting progression-free and overall survival in CLL patients and might be beneficial in countries with limited resources.
Revista Brasileira de Hematologia e Hemoterapia, 2009
Smudge cells, also known as Gumprecht cells 1 are ragged lymphoid cells found mainly in peripheral blood smears of patients with chronic lymphocytic leukemia (CLL) and other B-cell chronic lymphoproliferative diseases (CLD). Smudge cells are not simply artifacts of slide preparations and there is Smudge cells in peripheral blood smears did not differentiate chronic lymphocytic leukemia from other B-cell chronic lymphoprolipherative diseases Sombras nucleares no esfregaço do sangue periférico não diferenciam a leucemia linfocítica crônica das outras doenças linfoproliferativas B crônicas
It has recently been suggested that the percentage of smudge cells on blood smears from patients with chronic lymphocytic leukemia (CLL) could predict overall survival. However, smudge cells are a cytological artifact influenced by multiple physical factors not related to CLL. To identify simple parameters reflecting CLL cell fragility, we studied CD45 expression in a series of 66 patients with Binet stage A CLL. Decreased CD45 expression was specific for CLL cells when compared to 44 patients with a leukemic phase of B-cell non Hodgkin lymphoma and 42 control B-cells. CD45 expression was markedly decreased for all patients with CLL with high percentages of smudge cells. CLL cells with the lowest CD45 expression were the most sensitive to osmotic shock. Very low levels of CD45 expression were significantly associated with lack of CD38 expression, absence of trisomy 12, and with increased treatment free survival time. Altogether, these results demonstrate that low levels of CD45 expression are specific to CLL cells and reflect cell fragility, suggesting that this is an important intrinsic biological feature that determines disease course. Am. J. Hematol. 88:747–753, 2013. V C 2013 Wiley Periodicals, Inc.
Lymphocytosis with Smudge Cells Is Not Equivalent to Chronic Lymphocytic Leukemia
Case Reports in Oncology, 2021
Chronic lymphocytic leukemia (CLL) often presents with lymphocytosis and smudge cells (SCs) on routine peripheral blood (PB) tests. In some cases, these findings are assumed to be sufficient to diagnose CLL. We present a 54-year-old male who was referred for further management of progressing CLL. At the initial presentation, he looked unwell and had diffuse lymphadenopathy and splenomegaly. Blood work showed normocytic anemia (hemoglobin 72 g/L), thrombocytopenia (platelet count 74 × 10 9 /L), leukocytosis (white blood cell count 135.5 × 10 9 /L) including lymphocytosis (130.1 × 10 9 /L), and the presence of SCs on a PB smear. Additional workup including flow cytometry (FC), bone marrow biopsy, and lymph node biopsy led to a diagnosis of leukemic stage of advanced-stage mantle cell lymphoma. Although lymphocytosis with SCs is more frequently and in higher quantities seen in CLL they are not pathognomonic and can be present in a variety of lymphoproliferative disorders. Additional diagnostic examination of cell morphology and FC to assess clonality and determine the immunotype of lymphocytes are required to establish an accurate diagnosis and determine appropriate further management of the specific disease type.
Hematology, 2006
The individual prognosis of patients with chronic lymphocytic leukemia (CLL) is extremely variable. Although clinical stages remain the basis for assessing prognosis in CLL, a number of biological markers, particularly serum markers, cytogenetic abnormalities, IgVH mutations, CD38 and ZAP-70 expression in leukemic cells offer important, independent prognostic information. Before being incorporated into daily practice, however, these markers require standardization and validation in large, prospective trials. Meanwhile, treatment of patients with CLL not included in clinical studies should be decided on the basis of classical NCI/CLL Working Group criteria. An important area of research in CLL prognostication is the identification of markers useful for predicting response to therapy and its duration. Among them, del(17p), reflecting P53 abnormalities, is particularly important. Also relevant is del(11q), which points to ATM defects. There is also some correlation between IgVH mutatio...
Leukemia & Lymphoma, 2013
Chronic lymphocytic leukemia (CLL) is a clinically and biologically heterogeneous disease where the majority of patients have an indolent disease course, while others may experience a far more aggressive disease, treatment failure and poor overall survival. During the last two decades, there has been an intense search to fi nd novel biomarkers that can predict prognosis as well as guide treatment decisions. Two of the most reliable molecular prognostic markers, both of which are off ered in routine diagnostics, are the immunoglobulin heavy chain variable ( IGHV ) gene mutational status and fl uorescence in situ hybridization (FISH) detection of prognostically relevant genomic aberrations (e.g. 11q ؊ , 13q ؊ , ؉ 12 and 17p ؊ ). In addition to these markers, a myriad of additional biomarkers have been postulated as potential prognosticators in CLL, on the protein (e.g. CD38, ZAP70, TCL1), the RNA (e.g. LPL , CLLU1 , micro-RNAs) and the genomic (e.g. TP53 , NOTCH1 , SF3B1 and BIRC3 mutations) level. Eff orts are now being made to test these novel markers in larger patient cohorts as well as in prospective trials, with the ultimate goal to combine the " best " markers in a " CLL prognostic index " applicable for the individual patient. Although it is clear that these studies have signifi cantly improved our knowledge regarding both prognostication and the biology of the disease, there is still an immediate need for recognizing biomarkers that can predict therapy response, and eff orts should now focus on addressing this pertinent issue. In the present article, we review the extensive literature in the fi eld of prognostic markers in CLL, focus on the most clinically relevant markers and discuss future directions regarding biomarkers in CLL.