scholarly journals Recombinant alpha 2-interferon in the treatment of B chronic lymphocytic leukemia in early stages

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1295-1298
Author(s):  
C Rozman ◽  
E Montserrat ◽  
N Vinolas ◽  
A Urbano-Ispizua ◽  
JM Ribera ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Complete Response ◽  
Absolute Number ◽  
Peripheral Blood Lymphocytes ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Low Doses ◽  
The Absolute ◽  
Cell Chronic Lymphocytic Leukemia

Ten previously untreated patients with early B cell chronic lymphocytic leukemia (B-CLL) (seven in Rai's stage 0, three in stage I) were given recombinant alpha 2-interferon (alpha 2IF) (2 X 10(6) U/m2 intramuscularly three times a week for a minimum of 14 weeks) to assess its effectiveness. All patients were evaluable for response to therapy and toxicity. No complete response was achieved. In all cases a definite, although transient reduction in the absolute number of peripheral blood lymphocytes was observed. In eight patients an increase in the absolute number of granulocytes was detected. None of the patients experienced severe hematologic toxicity. Fatigue, malaise, and fever were the more common side effects, but all patients were able to finish their treatment as planned. The results of this pilot study suggest that low doses of recombinant alpha 2-IF have some activity in early and previously untreated B-CLL and that further studies of IF effectiveness in B-CLL seem warranted.

scholarly journals Recombinant alpha 2-interferon in the treatment of B chronic lymphocytic leukemia in early stages

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1295-1298 ◽  
Author(s):  
C Rozman ◽  
E Montserrat ◽  
N Vinolas ◽  
A Urbano-Ispizua ◽  
JM Ribera ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Complete Response ◽  
Absolute Number ◽  
Peripheral Blood Lymphocytes ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Low Doses ◽  
The Absolute ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Ten previously untreated patients with early B cell chronic lymphocytic leukemia (B-CLL) (seven in Rai's stage 0, three in stage I) were given recombinant alpha 2-interferon (alpha 2IF) (2 X 10(6) U/m2 intramuscularly three times a week for a minimum of 14 weeks) to assess its effectiveness. All patients were evaluable for response to therapy and toxicity. No complete response was achieved. In all cases a definite, although transient reduction in the absolute number of peripheral blood lymphocytes was observed. In eight patients an increase in the absolute number of granulocytes was detected. None of the patients experienced severe hematologic toxicity. Fatigue, malaise, and fever were the more common side effects, but all patients were able to finish their treatment as planned. The results of this pilot study suggest that low doses of recombinant alpha 2-IF have some activity in early and previously untreated B-CLL and that further studies of IF effectiveness in B-CLL seem warranted.

Unrelated Donor Marrow Transplantation for B-Cell Chronic Lymphocytic Leukemia After Using Myeloablative Conditioning: Results From the Center for International Blood and Marrow Transplant Research

2005 ◽  
Vol 23 (24) ◽  
pp. 5788-5794 ◽  
Author(s):  
Steven Z. Pavletic ◽  
Issa F. Khouri ◽  
Michael Haagenson ◽  
Roberta J. King ◽  
Philip J. Bierman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Cell Chronic Lymphocytic Leukemia

Purpose To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL). Patients and Methods A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients. Results Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively. Conclusion These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.

Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.

1997 ◽  
Vol 15 (2) ◽  
pp. 458-465 ◽  
Author(s):  
J M Sorensen ◽  
D A Vena ◽  
A Fallavollita ◽  
H G Chun ◽  
B D Cheson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
National Cancer Institute ◽  
Response Rate ◽  
Performance Status ◽  
Treatment Protocol ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Motor Dysfunction ◽  
Hematologic Toxicity ◽  
Contributing Factors

PURPOSE To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

Influence of Chromosomal Aberrations on Response to First Line Therapy in B-Cell Chronic Lymphocytic Leukemia: Interim Analysis of PALG-CLL3 Randomized Study Comparing Cladribine Plus Cyclophosphamide vs Fludarabine Plus Cyclophosphamide.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2046-2046
Author(s):  
Tadeusz Robak ◽  
Jerzy Z. Blonski ◽  
Ewa Wawrzyniak ◽  
Aleksandra Palacz ◽  
Joanna Gora-Tybor ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chromosomal Aberrations ◽  
Interim Analysis ◽  
Chromosomal Abnormalities ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Lower Probability ◽  
Trisomy 12 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Impact of cytogenetic abnormalities on treatment with different purine nucleoside analogs in patients (pts) with B-cell chronic lymphocytic leukemia (B-CLL) is largely unknown. One of objectives of PALG-CLL3 trial, comparing cladribine plus cyclophosphamide (CC) with fludarabine plus cyclophosphamide (FC) in previously untreated progressive B-CLL, was to verify the response to treatment in subsets of pts characterized by common cytogenetic abberrations. Chromosomal abnormalities were assessed using fluorescence in situ hybridization (FISH) on interphase nuclei of lymphocytes on whole blood smears prior to the start of the study treatment. Pts were screened for trisomy 12, deletions (del) 11q, del 13q and del 17p using DNA probes: CEP12, LSI: ATM, D13S319 and p53 (Vysis), respectively. For the purpose of the present interim analysis complete cytogenetic results were available in 133 pts out of 423 pts included to the study. In this group the chromosomal aberrations were detected in 102 pts (77%) including single abnormalities observed in 69 pts (52%) and two or more aberrations in 33 pts (25%). Thirty-one pts (23%) exhibited a normal interphase FISH pattern. The most frequent single abnormality was del 13q found in 38 pts (29%), while del 17p, trisomy 12 and del 11q were identified in 14 pts (11%), 11 pts (8%), and 6 pts, (5%), respectively. The most frequently observed associations of chromosomal aberrations were: del 13q with del 11q (11 pts, 8%) and del 13q with del 17p (10 pts, 8%). Four pts (3%) revealed three chromosomal abnormalities including association of trisomy 12/del 11q/del 13q in two pts, trisomy 12/del 11q/del 17p in one pt and del 11q/del 13q/del 17p in one pt. Overall, treatment was completed and response assessed in 113 out of 133 pts with known FISH pattern. In this group of pts del 17p was the only chromosomal abnormality that correlated significantly with treatment outcome. Pts with del 17p (21, 19%) had lower probability to achieve a complete response (CR) (0.044). Interestingly, in independent analyses of both treatment arms, the negative impact of 17p was seen in pts treated with FC (p=0.002), but not in pts treated with CC (p=0.6). Moreover, comparing response rates between treatment arms we found that CC was superior to FC in terms of complete response in pts with del 17p (57% CR in CC v 14% CR in FC arm, p=0.04). In conclusion, chromosomal abnormalities can be detected in majority B-CLL pts requiring treatment. Our preliminary results suggest that CC combination may have some advantage in terms of CR achievement in B-CLL pts harboring del 17p.

Rituximab Consolidation and Maintenance Immunotherapy Improve Outcome in B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2035-2035 ◽  
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Gianfranco Catalano ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
B Cell ◽  
Response Duration ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Monoclonal antibodies in combination with chemotherapy allowed us to obtain more responses and longer response duration in B-cell chronic lymphocytic leukemia (B-CLL), reducing disease burden to levels detectable only by flow cytometry. Moreover, it has been reported that low-dose rituximab decreases CD20 antigen loss via shaving and promotes enhanced targeting in CLL (Williams, 2006). We performed a phase II study that added rituximab to fludarabine (Flu) as therapy for symptomatic, untreated CLL. Remission status was assessed by a multiparametric flow cytometric method based on the detection of CD19+CD5+CD79b– residual B-CLL lymphocytes. VH mutational status, CD38, ZAP-70 and cytogenetics were obtained in all pts before treatment. We defined as “high risk” pts having at least two of the following markers: unmutated IgVH, CD38&gt;30%, ZAP-70&gt;20%, intermediate/unfavorable cytogenetics (trisomy 12 or del11q or del17p). Eighty-two CLL pts, median age 61 years, received six monthly courses of Flu (25 mg/m2 for 5 days) and four weekly doses of rituximab (375 mg/m2) starting after completion of Flu therapy. According to modified Rai stages, 8 pts had a low stage, 70 an intermediate stage and 4 a high stage. Based on NCI criteria, 66/82 (80%) pts achieved a complete remission (CR), 12/82 (15%) a partial remission (PR) and 4/82 (5%) no response or progression. Hematologic toxicity included mainly neutropenia (grade 3 and/or 4 in 42 pts) and thrombocytopenia (grade 3 and/or 4 in 4 pts). Thirty-five pts in clinical CR or PR, either with CD5+CD19+CD79b– bone marrow (BM) cells &gt;1% (MRD+, n=20 pts) or MRD negative but presenting CD5+CD19+ peripheral blood lymphocytes (PBL) &gt;1000/microl (n=15 pts) within 1 year after completion of the induction treatment, underwent consolidation/maintenance therapy with four monthly cycles of rituximab at 375 mg/m2 followed by twelve monthly doses of rituximab at 150 mg/m2. The median follow-up duration was 46 months. Noteworthy, all B-CLL pts experienced a long progression-free survival (PFS) from the end of induction treatment (68% at 5 years). Nevertheless, CLL pts that underwent consolidation and maintenance therapy (n=35) showed a significant longer response duration (85% at 5 years, Figure). On the other hand, BM and PBL persistently MRD negative (&gt;1 year) pts (n=29) showed a response duration similar to that of the consolidated pts (87% at 5 years). A significant shorter PFS was observed within CD38+ pts (39% vs 78% at 5 years, P=0.002), unmutated pts (45% vs 94% at 2.5 years, P=0.001) and ZAP-70+ pts (36% vs 88% at 6 years; P=0.00002). Notably, within the “high risk” subset (n=30), considering only MRD+ pts in CR or PR (n=20), MRD+ consolidated pts (n=11) showed a significant longer response duration (64% vs 13% at 2 years, P=0.006) in comparison with MRD+ unconsolidated pts (n=9). In conclusion, consolidation/maintenance therapy with rituximab prolongs significantly the response duration in B-CLL, improving also the outcome of the “high risk” subset. Figure Figure

Delayed and long-lasting complete response to fludarabine in two patients with B-cell chronic lymphocytic leukemia

1999 ◽  
Vol 78 (9) ◽  
pp. 435-436
Author(s):  
F. Zaja ◽  
D. Russo ◽  
L. Marin ◽  
F. Silvestri ◽  
M. Ramello ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Cell Chronic Lymphocytic Leukemia

Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1057-1063 ◽  
Author(s):  
Wendelina J. M. Mackus ◽  
Florine N. J. Frakking ◽  
Annette Grummels ◽  
Laila E. Gamadia ◽  
Godelieve J. de Bree ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
The Absolute ◽  
Cell Chronic Lymphocytic Leukemia

Abstract In patients with B-cell chronic lymphocytic leukemia (B-CLL), the absolute number of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n = 12; Rai I-II, n = 10; Rai III-IV, n = 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses. In all Rai stages a significant increase in the absolute numbers of CD3+ cells was observed. Whereas the number of CD4+ cells was not different from controls, patients with B-CLL showed significantly increased relative and absolute numbers of CD8+ cells, which exhibited a CD45RA+CD27- cytotoxic phenotype. Analysis of specific immune responses with tetrameric cytomegalovirus (CMV)–peptide complexes showed that patients with B-CLL had significantly increased numbers of tetramer-binding CMV-specific CD8+ T cells. The rise in the total number of CD8+ cytotoxic T cells was evident only in CMV-seropositive B-CLL patients. Thus, our data suggest that in patients with B-CLL the composition of T cells is shifted toward a CD8+ cytotoxic cell type in an effort to control infections with persistent viruses such as CMV. Moreover, they offer an explanation for the high incidence of CMV reactivation in CLL patients treated with T cell–depleting agents, such as the monoclonal antibody (mAb) alemtuzumab (Campath; α-CD52 mAb). Furthermore, because in CMV-seronegative patients no increase in cytotoxic CD8+ T cells is found, our studies do not support the hypothesis that tumor-specific T cells account for T-cell expansion in B-CLL.

scholarly journals Changes in Glycanic Determinants of Lymphocytes Membranes in Peripheral Blood in Patients with B-Cell Chronic Lymphocytic Leukemia under Antitumor Therapy

2021 ◽  
Vol 6 (6) ◽  
pp. 141-147
Author(s):  
G. S. Maslak ◽  
◽  
G. P. Chernenko ◽  
V. M. Baibakov ◽  
A. D. Viselko ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Cytostatic Therapy ◽  
Tn Antigen ◽  
Antitumor Therapy ◽  
Blood Lymphocytes ◽  
Cell Chronic Lymphocytic Leukemia

The purpose of the study was to study the nature of changes in the exposure of surface glycans of peripheral blood lymphocytes in patients with B-cell chronic lymphocytic leukemia under conditions of antitumor therapy. Materials and methods. We studied the features of exposure of surface glycotopes of peripheral blood lymphocytes in patients with B-cell chronic lymphocytic leukemia under conditions of antitumor therapy using a set of seven lectins labeled with FITC and monoclonal antibodies to Tn-antigen- FITC for the detection of Tn antigen and CD43 exposure on blood lymphocytes. Cytostatic therapy included cyclophosphamide, vincristine (oncovin), prednisolone. Data were recorded on a Beckman Coulter EPICS flow cytometer. The results were processed using FCS3 Express. Results and discussion. The number of lymphocytes of healthy donors with a positive reaction to ConA, PHA-L, SNA, MAA-II and α1-acid glycoprotein amounted to 16.0±3.0%, 23.0±2.3%, 15.0±1.5%, 25.0±1.8% and 15.0±1.3%, respectively. The number of LABA-, UEA I-positive lymphocytes was 0.90±0.03% and 2.9±0.2%, respectively, and there was no binding to antibodies to Tn- and CD43-antigens. In the blood of patients with chronic lymphocytic leukemia, the level of ConA-, SNA- and MAA-II-positive lymphocytes increased relative to control by 2.2, 3.7 and 2.6 times, respectively. The number of LABA- and UEA I-positive lymphocytes in patients with chronic lymphocytic leukemia increased by 11 (p <0.01) and 23 (p <0.001) times and amounted to 10.5±0.5% and 67.5±5.5% respectively. The number of lymphocytes with CD43 antigen on their surface increased by 72 times, and the Tn antigen increased by 80 times. Cytostatic therapy reduced the level of LABA- and UEA I-positive lymphocytes by almost half, and MAA II-positive cells and lymphocytes interacting with antibodies to CD43 and Tn antigen by a third. The level of PHA-L-positive lymphocytes in the blood of chronic lymphocytic leukemia patients after undergoing alkylating therapy increased by 18.0±2.0% and almost did not differ from those obtained in the control group. Conclusion. 1. In chronic lymphocytic leukemia patients, the structure of glycoconjugates in peripheral blood lymphocytes changes, manifested in increased exposure of L-fucose, α-mannose and N-acetylneuraminic acid, which is confirmed by a significant increase in relation to the control of the number of ConA-, SNA-, MAA-II-, LABA I-positive cells. 2. Patients with chronic lymphocytic leukemia showed a significant increase in the number of lymphocytes, in which the markers of carcinogenesis CD43 and Tn antigens were found. 3. Cytostatic therapy significantly reduced the level of LABA-, UEA I- and MAA II-positive cells, as well as partially Tn- and CD43-antigen-positive lymphocytes, which indicates its positive effect on the treatment of chronic lymphocytic leukemia

scholarly journals bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1820-1828 ◽  
Author(s):  
M Hanada ◽  
D Delia ◽  
A Aiello ◽  
E Stadtmauer ◽  
JC Reed
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Methylation Status ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Gene Rearrangements ◽  
Normal Peripheral Blood ◽  
Cell Chronic Lymphocytic Leukemia

Abstract The bcl-2 gene becomes transcriptionally deregulated in the majority of low-grade non-Hodgkin lymphomas as a result of t(14;18) translocations that place the bcl-2 gene at 18q21 into juxtaposition with the Ig heavy- chain locus at 14q32. This chromosomal translocation or similar bcl-2 gene rearrangements involving the Ig light-chain genes have been reported to occur in some cases of B-cell chronic lymphocytic leukemia (B-CLL). We analyzed the structure, methylation, and expression of the bcl-2 gene in 20 cases of B-CLL or closely related variants of this lymphoproliferative disorder, including at least 16 typical examples of CD5+ B-CLL. None of the 20 specimens had evidence of bcl-2 gene rearrangements, based on Southern blot analysis using three different bcl-2 probes. However, immunoblot analysis using antibodies specific for the Bcl-2 protein showed that 14 of 20 cases (70%) contained levels of p26-Bcl-2 that were equal to or greater than those found in a t(14;18)-bearing lymphoma cell line. Furthermore, in 19 of 20 cases (95%), the Bcl-2 protein was present at levels that were 1.7- to 25- fold higher than in normal peripheral blood lymphocytes. These differences in the relative levels of Bcl-2 protein among cases of B- CLL appeared to be functionally significant, in that a preliminary analysis of 3 representative cases showed that CLL cells with higher levels of Bcl-2 protein survived longer in culture and were delayed in their onset of DNA degradation relative to CLL cells with lower Bcl-2 protein levels. Evaluation of the methylation status of the bcl-2 gene using the isoschizomers Msp I and Hpa II, and a probe corresponding to the first major exon of the gene showed complete demethylation of both copies of the bcl-2 gene in a region corresponding to a 2.4-kb Msp I fragment in all 20 cases of B-CLL. In contrast, analysis of 6 of 6 B- cell lines that harbor a t(14;18) was consistent with hypomethylation of only one of the two bcl-2 alleles. Neither copy of the bcl-2 gene was demethylated in this region in 5 of 5 lymphoid cell lines that lack this translocation. However, hypomethylation of the bcl-2 gene did not necessarily correlate with the relative levels of Bcl-2 protein present in the B-CLL cells, suggesting that additional mechanisms for regulating bcl-2 expression are involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Flow Cytometric Detection and Phenotype of Circulating CD34+ Cells in Patients Affected by Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4329-4329
Author(s):  
Fabio Stagno ◽  
Nunziata Laura Parrinello ◽  
Giovannella Fargione ◽  
Anna Triolo ◽  
Antonella Privitera ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Flow Cytometric Analysis ◽  
Absolute Number ◽  
Lymphocytic Leukemia ◽  
Unexpected Finding ◽  
Advanced Stage ◽  
Flow Cytometric ◽  
Cd34 Cells ◽  
The Absolute

Abstract Flow cytometric determination of peripheral blood CD34+ cells provides reliable measurements of circulating hemopoietic progenitors. Since the detection of the absolute number of circulating CD34+ cells has been found of clinical utility in the setting of chronic myeloproliferative disorders, we investigated whether peripheral CD34+ cells could play any role in the clinical work-up of B-cell chronic lymphocytic leukemia (B-CLL). In this view, we determined by flow cytometry the absolute number of circulating CD34+ cells in the peripheral blood of 28 patients (16 males and 12 females, median age 67 years) affected by typical B-CLL (Matutes score 5,4,3) and in different Rai stages of the disease (19 early stage: Rai 0, I, II; 9 advanced stage: Rai III, IV). Conventional and multiparameter flow cytometric analysis was performed utilizing a FACSCalibur cytometer (Becton Dickinson). Our data showed a significant increase in the number of circulating CD34+ cells in the peripheral blood of patients with B-CLL (median CD34+ cells:7.8mL) as compared to controls (median CD34+ cells 0.1mL) (p=0.008). No statistical difference between B-CLL patients in early versus advanced stage (p=0.5) and between untreated versus treated (p=0.7) was found, as well as there was no correlation with some of the clinical characteristics of B-CLL (WBC-count, LDH levels, Beta-2M). In 10 out of 28 B-CLL affected patients, circulating CD34+ cells were correlated with ZAP-70 and CD38 antigen but no correlation was found. In addition, we detected in the peripheral blood of 22 out of 28 patients small numbers of circulating CD34+ cells displaying the CD19+/CD5+ phenotype (median CD34+/CD19+/CD5+ cells:5.7mL) whereas these cells were absent in normal controls. This unexpected finding, whose significance remains to be clarified and still restricted to a small number of cases, could be directly correlated to the underlying lymphproliferative disease and might represent a pool of leukemic stem cells. However, further studies are warranted.

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