RESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may complicate hematologic malignancies. HLH and malignancies have common clinical features, and HLH diagnostic criteria (HLH-2004/Hscore) were not validated in this specific population. We describe a case of a 72-year-old patient with a history of chronic lymphocytic leukemia stable for over 10 years who presented with fever and cytopenia. After excluding infectious etiologies and the progression of her disease, HLH was diagnosed. The patient was treated with etoposide, dexamethasone, intravenous immunoglobulin, and rituximab. Despite initial clinical improvement, the patient deteriorated and developed pulmonary aspergillosis and CNS involvement that reflected uncontrolled HLH. The patient died 45 days after her presentation. An unusual feature of this case was that HLH was not triggered by infection, disease transformation, or treatment. This case emphasizes the challenges of differentiating the development of overwhelming HLH from other complications associated with hematologic malignancy.
Assuntos
Leucemia Linfocítica Crônica de Células B , Linfo-Histiocitose Hemofagocítica , Idoso , Etoposídeo/uso terapêutico , Feminino , Febre , Humanos , Imunidade , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnósticoRESUMO
Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single-arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL. Forty patients received LD-FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression-free survival (PFS) was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment-related neutropenia occurred in 20 (47.6%) patients. During the entire study follow-up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non-neutropenic infections. In conclusion, LD-FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both "time and cost limited" and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high-risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Israel/epidemiologia , Masculino , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivadosRESUMO
BACKGROUND: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. AIMS: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL. RESULTS: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months. CONCLUSION: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.
Assuntos
Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias Leves de Imunoglobulina/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prognóstico , Modelos de Riscos Proporcionais , Tempo para o TratamentoRESUMO
Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre-existing chronic lymphocytic leukemia (CLL). Data on RS is sparse and mostly derived from case reports or small series of patients and only a few larger cohorts have been published. The purpose of this large retrospective study was to summarize our national experience with RS in CLL, examine possible risk factors, and analyze relevant demographic, laboratory and clinical parameters, including results of therapy and outcome. We first evaluated data obtained from 119 patients with RS diagnosed during 1971-2010 from 12 medical centers in Israel. The final cohort summarized consisted of 81 patients with RS who developed only diffuse large B-cell lymphoma (DLBCL) after exclusion all cases with insufficient data and those who were not DLBCL. Median overall survival from time of diagnosis of RS was 8 months; after applying the Richter score, patients could be stratified into three prognostic groups, while all other clinical and laboratory parameters evaluated had no prognostic significance. Prior therapy for CLL had no impact on RS survival (P = 0.8) and patients with therapy "naïve" RS and those who had already received chemotherapy prior to developing RS, had the same survival. The addition of rituximab to chemotherapy for RS improved 2 years overall survival from 19% in the chemotherapy alone arm to 42% (P value of 0.001). Although prognosis of patients with RS remains dismal, this retrospective observation provides support for the use of chemo-immunotherapy in DLBCL-RS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Terapia Combinada , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Israel/epidemiologia , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Contagem de Leucócitos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Rituximab , Terapia de Salvação , Índice de Gravidade de Doença , Avaliação de Sintomas , Síndrome , Resultado do TratamentoRESUMO
BACKGROUND: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL. METHODS: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL. RESULTS: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated ß2-microglobulin < 4000 µg/mL (P = .048), and the presence of 11q deletion (P = .0015). CONCLUSIONS: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications.
Assuntos
Medula Óssea/patologia , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/patologia , Mielofibrose Primária/diagnóstico , Reticulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/complicações , Medula Óssea/química , Exame de Medula Óssea , Cromossomos Humanos Par 11 , Corantes , Feminino , Deleção de Genes , Humanos , Israel/epidemiologia , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Coloração pela Prata/métodos , Trombocitopenia/sangue , Trombocitopenia/complicações , Microglobulina beta-2/sangueRESUMO
An insect-bite-like reaction is known to occur in patients with chronic lymphocytic leukemia (CLL). Most of the literature, however, consists of isolated case reports or small case series. The aim of this retrospective study was to review the national experience with insect-bite-like reaction in a large group of patients with CLL. The study cohort of patients with these skin reactions consisted of 48 patients (25 males, 23 females) of mean age 64.8 yr (range 33-89) at skin eruption. Data on clinical, histologic, immunophenotypic, and cytogenetic characteristics, treatment, and outcome were collected from the medical files. Mean time between diagnosis of CLL and appearance of the skin lesions was 3.1 yr (range -4 to 14 yr). The eruption was not related to disease activity or the course of the hematological disease. The eruption preceded the diagnosis of CLL in 10 patients (by 0-4 yr); and followed the diagnosis in 36; in 11 patients, it occurred during therapy for CLL and in nine after therapy. Mean duration of the skin findings was 21.5 months (range 0.3-132). The eruption usually presented in summer, although it occurred also at other times of the year, and predominantly affected the upper and lower limbs, although it also appeared on unexposed areas. Treatment included local ointments, antihistaminics, oral steroids, antibiotics, phototherapy, and dapsone with varying responses. Insect-bite-like reactions is a relatively common and disturbing skin reaction in CLL patients, it may be related to the immune dysregulation accompanying CLL and further exacerbated by external factors, including actual insect bites, chemoimmunotherapy, and pyogenic infection.
Assuntos
Mordeduras e Picadas de Insetos/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Dermatopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/imunologia , Exantema/patologia , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Prurido/diagnóstico , Prurido/tratamento farmacológico , Prurido/imunologia , Prurido/patologia , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Dermatopatias/patologia , Esteroides/uso terapêuticoRESUMO
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.
Assuntos
Convertases de Complemento C3-C5/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfoide/metabolismo , Western Blotting , Ativação do Complemento/genética , Ativação do Complemento/fisiologia , Complemento C5a/genética , Complemento C5a/fisiologia , Complexo de Ataque à Membrana do Sistema Complemento/genética , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfoide/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Major advances in the treatment of patients with hairy cell leukemia (HCL) have been made following the introduction of purine analogues. The major significant short-term toxicity of cladribine therapy are neutropenia and neutropenic fever (NF) which may be life-threatening. AIM: In this retrospective study, we compared the incidence and duration of neutropenia and hospitalization in patients with HCL treated with cladribine followed by peg-filgrastim as primary prophylaxis versus daily filgrastim given "on demand" according to absolute neutrophil count (ANC). METHODS: Medical records of patients with HCL diagnosed and followed in 12 medical centers in Israel during 1985-2015 were examined for details of disease at diagnosis. The efficacy of peg-filgrastim and filgrastim was assessed by evaluating the incidence of neutropenia (ANC < 1.0 × 10 [9]/L), number and length of hospitalizations, and number of days from the last day of therapy to recovery of ANC to >1.0 × 10 [9]/L. RESULTS: The study population included 202 patients with HCL, 159 of whom (80.7%) were treated with cladribine; 78 patients (49%) required hospitalization for the administration of broad-spectrum antibiotics due to NF. Twenty-eight (19%) patients were treated with peg-filgrastim as primary prophylaxis, while 74 (64%) received filgrastim "on demand" due to neutropenia. Median length of hospitalization, and nadir duration were 8 and 18 days respectively (p = 0.71, p = 0.44). CONCLUSIONS: Infectious complications post-cladribine treatment remain high. No difference was found in terms of incidence of NF, number of febrile days, and nadir duration in patients receiving primary peg-filgrastim prophylaxis compared to filgrastim given on demand. Both approaches are justifiable, and the choice remains at the physician's discretion.
Assuntos
Antineoplásicos/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Cladribina/efeitos adversos , Filgrastim/uso terapêutico , Leucemia de Células Pilosas/patologia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/etiologia , Neutropenia Febril Induzida por Quimioterapia/mortalidade , Neutropenia Febril Induzida por Quimioterapia/patologia , Cladribina/administração & dosagem , Feminino , Humanos , Israel , Tempo de Internação/estatística & dados numéricos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Profilaxia Pré-Exposição/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND/AIM: In this retrospective study, we summarized the national Israeli experience with hairy cell leukemia (HCL) in a large cohort of patients with a long follow-up. PATIENTS AND METHODS: Demographic data, and relevant laboratory and clinical parameters were analyzed, emphasizing the outcome after first-line treatment with cladribine. RESULTS: Data on 203 patients was collected from 12 medical centers during 1985-2015. Mean and median follow-up were 7.5 years and 5.18 years (interquartile range=0.1-40 years), and 5- and 10-year survival were 96% and 90.62%, respectively. The median age of diagnosis was 55.5 years for Jews and 49 years for Arabs (p=0.021), and most patients were males (81.77%); 52.2% were Ashkenazi Jews, 36.1% Sephardic Jews and 11.7% were Arab, Druze or other ethnicity. Cladribine was given to 159 patients (80.7%%) and most (62%) received intravenous (i.v.) and 38% received subcutaneous (s.c.) therapy. Overall survival and time to next treatment were not significantly different between the two schedules (i.v., s.c.). In univariate analysis of a variety of factors, only age >65 years had a negative impact on outcome, with shorter overall survival. It is of interest that Arab patients with HCL were diagnosed at an earlier age, but had a similar clinical course and outcome to both Ashkenazi and Sephardic Jews.
Assuntos
Antineoplásicos/administração & dosagem , Cladribina/administração & dosagem , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/etnologia , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Detecção Precoce de Câncer , Feminino , Humanos , Injeções Subcutâneas , Israel/etnologia , Leucemia de Células Pilosas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tempo para o Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Despite several advances in therapeutic options, the disease remains incurable. Recently, it was repeatedly demonstrated that statins, competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have antineoplastic effects. Therefore we aimed to study the effects of simvastatin (Sim) on malignant B cells derived from patients with CLL and mechanisms of action of the drug. METHODS AND RESULTS: Purified B-CLL cells from 15 patients were cultured either alone or with Sim at concentrations of 10, 50, and 100 microM. Viability, measured by the activity of mitochondrial dehydrogenases, was reduced significantly in the cells treated with Sim at 50 and 100 microM for 24 hours (p<0.005). The level of apoptosis, as measured by annexin binding to exposed phosphatidylserine moieties, increased significantly in the treated cells at concentrations higher than 50 microM for 24 hours (p<0.003). The level of necrosis, as measured by propidium iodide internalization, increased significantly after 24 hours exposure to Sim at 50 microM (p<0.01). The apoptotic cascade was studied by immunoblot analysis of caspases following Sim treatment. These showed cleavage of caspases 9, 8, and 3. Addition of the caspase inhibitor Z-VAD.fmk inhibited caspase 8 and 3 significantly but did not affect caspase 9. CONCLUSION: Exposure of clonal B lymphocytes from patients with CLL to simvastatin decreases viability significantly by the induction of apoptosis. The apoptosis induced by Sim is probably initiated by the mitochondrial caspase 9, which indirectly leads to activation of caspase 3 and 8.
Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Leucemia Linfocítica Crônica de Células B/enzimologia , Leucemia Linfocítica Crônica de Células B/patologia , Sinvastatina/farmacologia , Caspase 3 , Caspase 8 , Caspase 9 , Ativação Enzimática/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sinvastatina/uso terapêutico , Células Tumorais CultivadasRESUMO
BACKGROUND: Richter syndrome (RS) is the development of an aggressive lymphoid malignancy, in chronic lymphocytic leukemia (CLL). Most are diffuse large B-cell lymphomas (DLBCL), however in 10-15% of RS, there is transformation to Hodgkin lymphoma, termed "Hodgkin variant" (HV). In the present retrospective study we summarize the Israeli experience with HV-RS, and analyze demographic data, relevant laboratory and clinical parameters, and outcome. PATIENTS AND METHODS: We collected and analyzed data from 119 patients with RS from 12 Centers in Israel during 1996-2010 and identified 16 cases with "Hodgkin's variant". RESULTS: The median age was 58 years, and 67% were males. The median time from CLL diagnosis to development of HV was 5.9 (range=0.8-11.9) years and the median survival was 39.5 months, compared to 9 months for the cases with RS-DLBCL. CONCLUSION: Hodgkin variant appears to differ from DLBCL-RS and is clinically less aggressive. However, compared to de novo Hodgkin's lymphoma, HV-RS has a worse prognosis.
Assuntos
Transformação Celular Neoplásica/patologia , Doença de Hodgkin/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Feminino , Humanos , Israel , Leucemia Linfocítica Crônica de Células B/terapia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Clonal B-lymphocytes of chronic lymphocytic leukemia (B-CLL) are characterized by decreased sensitivity to programmed cell death and, therefore, they accumulate in vivo. However, these malignant cells die rapidly in vitro. In the current study we concentrated on the contribution of autologous serum (AS) and lymphocyte subsets to the survival of the malignant cells in vitro. METHODS: Mononuclear cells from the peripheral blood of 26 CLL patients and 24 controls were incubated overnight in the presence or absence of AS and heat-inactivated AS (HI-AS) or fetal calf serum (FCS). Also, isolated B cells were incubated at different concentrations in the presence of AS and/or isolated T cells. The level of apoptosis of CD19+ cells was measured by flow cytometry. RESULTS: Spontaneous apoptosis of unfractionated B-CLL cells incubated with AS, FCS or without serum was significantly lower than the rate of B-cell death in the control group, in similar culture conditions. AS had an antiapoptotic effect on unfractionated B-CLL cells when compared with FCS. The rate of apoptosis of B-CLL cells was directly associated with stage. HI of AS had a variable effect, which was related to the stage of the disease. High concentrations of B cells and the addition of autologous T cells reduced the rate of apoptosis when incubated without serum. The antiapoptotic effect of T cells was most prominent in progressive stages. CONCLUSIONS: B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression.