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  • American Society of Hematology  (10)
  • 2000-2004  (10)
  • 1
    Online Resource
    Online Resource
    An IELSG International Survey of Primary Effusion Lymphoma (PEL).
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 3265-3265
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 3265-3265
    Abstract: PEL is a rare B-cell neoplasm characterized by a preferential involvement of fluid-filled body spaces, consistent infection of the tumor clone by human herpesvirus type-8 (HHV-8) and a close relationship with underlying immunodeficiency status of the host. The International Extranodal Lymphoma Study Group (IELSG) coordinated a retrospective survey involving 15 international institutions to determine the clinico-pathological features and patterns of outcome of PEL. Fourty-three patients (38 males and 5 females) were registered. Median age at diagnosis was 59 years (range 27–102). In 23 (53%) patients an associated human immunodeficiency virus (HIV) infection was reported, in one case the diagnosis of PEL was made after a solid organ transplantation, in two patients other immunodeficiency conditions were present. The tumor HHV-8 infection was demonstrated in 35 out of the 39 tested cases, Epstein-Barr virus infection in 13 of 30 cases. CD4 count was lower than 200/μl in 18 of the 25 cases in whom the data was available. An ECOG perfomance status score ≥ 2 was observed in 29 patients and the presence of B-symptoms in 20 patients. Serum LDH was elevated in 21 of the 39 tested patients. In 4 patients nodal involvement at diagnosis was reported, in 4 cases at least one extranodal site of localization other than serous cavities was present. A low/low-intermediate risk score according to International Prognostic Index was reported in 10 cases, an intermediate-high/high risk score in 29 cases. Twenty-one patients received systemic chemotherapy, in 17 cases an anthracycline-based regimen. Intrapleural cidofovir was administered in 3 patients. Twelve HIV+ patients received highly active anti-retroviral therapy (HAART), four of them as single therapy. Among the 39 patients for whom adequate follow-up data were available, median overall survival was 6.7 months, median cause-specific survival was 13.6 months and median progression-free survival was 8.3 months. Interestingly, cases of tumor complete regression after implementation of the sole HAART, after intrapleural administration of cidofovir or without any treatment were reported. Our data confirm the poor prognosis of PEL but suggest a possible heterogeneity of this entity with respect to its biological and clinical features. A review of the pathological, phenotypical and virological features is forthcoming to validate these preliminary results.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.3265.3265
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
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    Online Resource
    CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas
    American Society of Hematology ; 2002
    In:  Blood Vol. 100, No. 13 ( 2002-12-15), p. 4602-4608
    Details
    In: Blood, American Society of Hematology, Vol. 100, No. 13 ( 2002-12-15), p. 4602-4608
    Abstract: The CHK2 gene codifies for a serine/threonine kinase that plays a central role in DNA damage response pathways. To determine the potential role of CHK2 alterations in the pathogenesis of lymphoid neoplasms we have examined the gene status, protein, and mRNA expression in a series of tumors and nonneoplastic lymphoid samples. A heterozygous Ile157Thr substitution, also present in the germ line of the patient, was detected in a blastoid mantle cell lymphoma (MCL). CHK2 protein and mRNA expression levels were similar in all types of lymphomas and reactive samples, and these levels were independent of the proliferative activity of the tumors. However, 5 tumors, one typical MCL, 2 blastoid MCLs, and 2 large cell lymphomas, showed marked loss of protein expression, including 2 samples with complete absence of CHK2 protein. These 2 lymphomas showed the highest number of chromosomal imbalances detected by comparative genomic hybridization in the whole series of cases. However, no mutations, deletions, or hypermethylation of the promoter region were identified in any of these tumors. mRNA levels were similar in cases with low and normal protein expression, suggesting a posttranscriptional regulation of the protein in these tumors. CHK2 gene and protein alterations were not related to p53 and ATMgene status. In conclusion, CHK2 alterations are uncommon in malignant lymphomas but occur in a subset of aggressive tumors independently of p53 or ATM alterations. The high number of chromosomal imbalances in tumors with complete absence of CHK2 protein suggests a role of this gene in chromosomal instability in human lymphomas.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2002-04-1078
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2002
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
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    Online Resource
    Manteinance Treatment with Interferon (IFN) Is Not Necessary to Achieve Prolonged Progression Free Survival (PFS) in Patients with Indolent Non Hodgkin’s Lymphoma (NHL). Results from a Prospective Randomized Trial on 165 Patients.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1392-1392
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1392-1392
    Abstract: INTRODUCTION. Treatment with IFN and chemotherapy induces a significant improvement of PFS in patients with low-grade NHL, specially in patients with responsive disease. However, the best IFN schedule is still pending as benefits are observed when IFN is administered associated to the induction therapy or, as maintenance treatment or, in both treatment phases. OBJETIVE. To evaluate the additional benefit or not of one year maintenance treatment with IFN in patients who achieve response after an induction treatment with CVP and IFN for 3 months. PATIENTS & METHODS. From February 1990- October 2002, 165 patients with low-grade NHL were recruited. Patients received treatment with CVP (median number 6 cycles) and IFN, 3MU/m2 three times a week during 3 months. Patients with complete or partial responses were then randomized to receive treatment with 12 months of IFN, 3MU/m2 three times a week vs observation. With a median of 4,7 years (range 0.3 to 11.7 years) for surviving patients, we analysed response, PFS and overall survival. RESULTS. Patients median age was 63 years (range 28–89 years), with 65.5% having follicular (FL), 20% small lymphocyte and 14% marginal zone lymphoma. Most patients (83%) were in advance stage and 75% had extranodal involvement. Thirty-three percent of FL patients had a FLIPI index score 〉 3. Dose-intensity for cyclophosphamide and IFN in the induction treatment was 71% and 69%, respectively. Ten patients withdraw the study due to grade 3–4 toxicity events (6.5%). Response : 86% of patients achieved a response, 80% complete. One hundred and twelve out of the 143 responding patients were randomised to receive IFN for 12 months (56 patients) vs observation (56 patients). Patients and disease characteristics for each group were similar. Median dose of maintenance IFN treatment was 67% (range 8%–113%). Fourteen patients (25%) withdraw the study, 7 due to IFN toxicity. PFS : Median PFS of the whole series was 6.76 years, 6.6 years for patients in the maintenance IFN group vs 7.8 years for the observation group, p=0.7. Overall survival at 12 years is 81% for both groups. Interestingly, 31 patients who achieved a good response but were not randomised showed a significantly shorter OS, p=0.001. CONCLUSION. No additional increase on PFS has been observed when maintenance IFN is administered to patients responding to CVP and short term IFN induction therapy. With our data, very good response rates and long lasting remission are achieved with only 3 months IFN treatment. Treatment tolerance is therefore significantly better.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.1392.1392
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
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    Online Resource
    Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
    American Society of Hematology ; 2003
    In:  Blood Vol. 101, No. 7 ( 2003-04-01), p. 2489-2495
    Details
    In: Blood, American Society of Hematology, Vol. 101, No. 7 ( 2003-04-01), p. 2489-2495
    Abstract: A retrospective survey of patients with pathologically reviewed extragastric mucosa-associated lymphoma tissue (MALT) lymphomas from 20 institutions was performed. A total of 180 patients with histologically confirmed diagnosis of extragastric MALT lymphomas were studied. Their median age was 59 years (range, 21-92 years). Ann Arbor stage I disease was present in 115 patients (64%) and stage II disease in 16 (9%). Most cases were in the low or low-intermediate risk groups according to the International Prognostic Index (IPI). Forty-one (23%) patients had involvement of more than one extranodal site at diagnosis and in 24 cases (13%) the lymphoma presented at multiple mucosal sites (9 of them with only mucosal involvement, without bone marrow or nodal disease). Lymph node involvement was present in 21%. Patients were treated with a variety of therapeutic strategies, including chemotherapy in 78 cases. The median overall survival (OS) was not reached; the 5-year OS rate was 90% (95% CI, 82%-94%), the 5-year cause-specific survival (CSS) was 94% (95% CI, 87%-97%), and the 5-year progression-free survival (PFS) was 60% (95% CI, 50%-70%). Multivariate analysis showed that Ann Arbor stage was significantly associated with longer OS, nodal involvement with longer CSS, and favorable IPI score with better PFS. At a median follow-up of 3.4 years, 48 patients (27%; 95% CI, 20%-34%) had a relapse, 6 (3%; 95% CI, 1%-7%) showed histologic transformation, and 18 (10%; 95% CI, 6%-15%) experienced the development of a second tumor. Our data confirm the indolent nature of nongastric MALT lymphomas and the high rate of patients presenting with disseminated disease, which, when limited to mucosal sites, was not associated with a poorer outcome.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2002-04-1279
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2003
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
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    Online Resource
    Significance of a Single Human Leukocyte Antigen Mismatch on the Outcome of Nonmyeloablative Allogeneic Stem Cell Transplantation from Related Donors Using the Mexican Schedule.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 5182-5182
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5182-5182
    Abstract: The Mexican approach was used to conduct nonmyeloablative stem cell transplantation (SCT) in patients with various malignant and non-malignant hematologic diseases. Patients received a modified, low-intensity conditioning regimen, which included oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily staring on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Allografts were prospectively performed in 58 patients using sibling donors that were either human leukocyte antigen (HLA) identical (6/6) or compatible with 1 mismatch (5/6). In allografts where the donor was an HLA identical sibling (n = 40), the median overall survival was 33 months compared to 8 months when the donor was an HLA compatible sibling (n = 18; P 〈 .01). The 52-month survival was 47% versus 38% in patients receiving allografts from HLA-identical donors and HLA-compatible donors, respectively. The prevalence of acute graft-versus-host-disease (GVHD) was 57% versus 38%, the prevalence of chronic GVHD was 25% versus 11%, and the relapse rate was 45% versus 55% in patients receiving allografts from HLA-identical donors and HLA-compatible donors, respectively. Two patients failed to engraft; both were 5/6 matches. Despite a trend toward less favorable results in patients allografted from HLA compatible (5/6) siblings, most differences in outcome were not significant, likely due to the small number of patients in the study. These data suggest that nonmyeloablative SCT using the Mexican approach may be a valid option for individuals with either an HLA identical or HLA compatible sibling donor.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.5182.5182
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
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    Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma
    American Society of Hematology ; 2003
    In:  Blood Vol. 101, No. 1 ( 2003-01-01), p. 78-84
    Details
    In: Blood, American Society of Hematology, Vol. 101, No. 1 ( 2003-01-01), p. 78-84
    Abstract: To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center–CD10+ (GC-CD10+; CD10+/Bcl-6+/MUM1−/CD138−), germinal center–CD10− (GC-CD10−; CD10−/Bcl-6+/ MUM1−/CD138−), post–germinal center (pGC; CD10−/bcl-6±/ MUM1+/CD138−), and plasmablastic (CD10−/bcl-6−/MUM1+/CD138+). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10+, 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10+ tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10− patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2002-04-1286
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2003
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
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    Online Resource
    Spontaneous and drug-induced apoptosis is mediated by conformational changes of Bax and Bak in B-cell chronic lymphocytic leukemia
    American Society of Hematology ; 2002
    In:  Blood Vol. 100, No. 5 ( 2002-09-01), p. 1810-1816
    Details
    In: Blood, American Society of Hematology, Vol. 100, No. 5 ( 2002-09-01), p. 1810-1816
    Abstract: The role of Bax and Bak, 2 proapoptotic proteins of the Bcl-2 family, was analyzed in primary B-cell chronic lymphocytic leukemia (CLL) cells following in vitro treatment with fludarabine, dexamethasone, or the combination of fludarabine with cyclophosphamide and mitoxantrone (FCM). A strong correlation was found between the number of apoptotic cells and the percentage of cells stained with antibodies recognizing conformational changes of Bax (n = 33;r = 0.836; P 〈 .001) or Bak (n = 10;r = 0.948; P 〈 .001). Preincubation of CLL cells with Z-VAD.fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone), a broad caspase inhibitor, abolished caspase-3 activation, exposure of phosphatidylserine residues, and reactive oxygen species generation; partially reversed the loss of transmembrane mitochondrial potential (ΔΨm); but did not affect Bax or Bak conformational changes. These results indicate that the conformational changes of Bax and Bak occur upstream of caspase activation or are caspase independent. Following drug-induced apoptosis, Bax integrates into mitochondria, as demonstrated by fluorescence microscopy and Western blot, without changes in the total amount of Bax or Bak protein. Fludarabine and FCM induce p53 stabilization, but do not seem to be essential in inducing Bax and Bak conformational changes, as they are also observed in dexamethasone-treated CLL cells. These results demonstrate that, in CLL cells, the change in the intracellular localization of Bax from cytosol to mitochondria and the conformational changes of Bax and Bak are among the early steps in the induction of cell death.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2001-12-0327
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2002
    detail.hit.zdb_id: 1468538-3
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  • 8
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    Clinical Characteristics and Outcome of a Large Series of Patients with Chronic Lymphocytic Leukemia (CLL) According to ZAP-70 Expression.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 14-14
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 14-14
    Abstract: The prognosis of patients with CLL has been traditionally assessed by using clinical stages. Clinical stages, however, are a mere reflection of the biological diversity of CLL. In this regard, we and others have recently shown that ZAP-70 expression separates CLL into two clinical forms with different outcome. The aim of this study was to analyze the distribution of age, gender, and different prognostic parameters according to ZAP-70 expression in 222 pts with CLL (median age, 62 yrs; female/male: 89/133). ZAP-70 was determined by flow cytometry, a high expression being defined as & gt;20% ZAP-70 positive CLL cells. Median follow-up of the series was 7.1 years. Clinical stages at diagnosis were: Binet stage A, 187 pts; B, 21 pts; and C, 14 pts. Rai Stage 0, 123 pts; I, 53 pts; II, 28 pts; III, 7 pts; and IV, 11 pts. Overall median survival was 13 years. Parameters associated with a high ZAP-70 expression were lymphocyte doubling time & gt;12 mos., atypical morphology, bone marrow infiltration & gt; 60%, increased serum LDH and timidin kinase, CD38 expression & gt;20%, del(13q14), unmutated status of IgVH, and development of Richer syndrome. Interestingly, ZAP-70 expression distribution correlated with Rai’s stage (0 vs. 1 to 4). Also, CD38 expression was able to separate two subpopulations with different survival among CLL cases with low ZAP-70 expression (median survival 18 yrs vs. 13 yrs), but not in pts. with ZAP-70 & gt;20%. About 50% of pts in Binet A progressed during the follow-up. Median time to progression for patients with high ZAP-70 expression was 3.3 years whereas it was not reached for patients with low ZAP-70 expression. Median survival of pts with low ZAP-70 expression was 16.3 years, whereas it was of 8.5 years in those with high ZAP-70 expression. In conclusion, ZAP-70 expression identifies a subgroup of patients with CLL with unfavorable prognostic factors related to the proliferation and progression of the disease. Prognostic Parameters according to ZAP-70 expression Variable ZAP-70 & gt;20% ZAP-70 & lt; 20% p= Median age 60 yrs 63 yrs Gender (female) 39% 41% LDT & lt; 12 mos 42% 23% 0.009 Atypical morphology 54% 12% 0.000 BM infiltration & gt;60% 50% 33% 0.03 Increased LDH 13% 4% 0.028 Increased TK 66% 28% 0.000 CD38 & gt; 20% 67% 32% 0.000 Del(13q14) 38% 55% 0.027 Unmutated IgVH 88% 11% 0.000 Richter Syndrome 8% 2% 0.039 Rai Stage & gt; 0 53% 37% 0.039 TTP (Binet A) 3.3 yrs NR 0.000 Median Survival 16.3 yrs 8.5 yrs 0.000
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.14.14
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
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  • 9
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    Quantitative PCR Predicts Early Relapse in Patients with Chronic Lymphocytic Leukemia (CLL) Submitted to Autologous Stem Cell Transplantation. The Case for Early Clinical Intervention.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2255-2255
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2255-2255
    Abstract: Autologous stem cell transplants (auto-SCT) are increasingly performed in patients with CLL. Although this procedure results in a high complete response (CR) rate, most patients eventually relapse. The median time to relapse is around 5 years. Increasing levels of minimal residual disease (MRD), detected by PCR or flow cytometry (FC) are associated with clinical relapse. The early detection of patients likely to relapse shortly after SCT may be useful in the management of these patients. With this background, we analyzed the levels of MRD and its correlation with the risk of relapse and clinical outcome in 19 patients with CLL submitted to auto-SCT. MRD was assessed by FC and quantitative real time PCR of the IgH region using allele-specific oligonucleotides (ASO-PCR) in peripheral blood and/or bone marrow DNA samples obtained before SCT and at different time points thereafter. After SCT, 17 patients achieved CR and 2 partial response. A continuous pattern of relapses was observed and, after a median follow-up of 48 months (range, 11–101), 11/19 patients have progressed. The median number of CLL cells detected prior to SCT was 2.4x10−2 decreasing to 5.31x10−4 at 3–6 months after auto-SCT. No further decrease was observed beyond that point. At 3–6 months after auto-SCT, only 3/17 patients in CR had undetectable levels of disease. Patients with a MRD level 〉 10−3 at this time point (3–6 months after transplant) had a significantly higher risk of progression than those who had less than 10−3 CLL cells. All but one patients with MRD 〉 10−3 have relapsed (7/8) whereas only 4/9 with MRD 〈 10−3 did so. As shown in the figure, median time to progression was significantly shorter in those patients with a higher MRD level (16 vs. 55 months; p=0.003) Figure Figure In conclusion, quantification of MRD within the first 6 months after auto-SCT allows the identification of CLL patients with a high risk of early clinical relapse. These data provide background to investigate whether early treatment, before clinically overt relapse occurs, might be useful in patients with high risk of relapse after SCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2255.2255
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
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  • 10
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    Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species
    American Society of Hematology ; 2001
    In:  Blood Vol. 98, No. 9 ( 2001-11-01), p. 2771-2777
    Details
    In: Blood, American Society of Hematology, Vol. 98, No. 9 ( 2001-11-01), p. 2771-2777
    Abstract: Mechanisms involving the in vitro effect of rituximab in cells from 55 patients with B-cell lymphoproliferative disorders were investigated. No cytotoxic effect was observed when cells were incubated with rituximab alone, but in the presence of human AB serum rituximab induced complement-dependent cell death (R-CDC). A cytotoxic effect was observed in cells from 9 of 33 patients with B-cell chronic lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of 4 patients with follicular lymphoma, and 2 of 2 patients with hairy-cell leukemia. R-CDC was observed in cells from patients expressing more than 50 × 103 CD20 molecules per cell, and directly correlated with the number of CD20 molecules per cell. Preincubation with anti-CD59 increased the cytotoxic effect of rituximab and sensitized cells from nonsensitive cases. Neither cleavage of poly-ADP ribose polymerase (PARP) nor activation of caspase-3 was observed in R-CDC. In addition, no cells with a hypodiploid DNA content were detected and R-CDC was not prevented by a broad-spectrum caspase inhibitor, suggesting a caspase-independent mechanism. Incubation with rituximab in the presence of AB serum induced a rapid and intense production of reactive oxygen species (ROS). R-CDC was blocked by the incubation of cells with N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that the cytotoxic effect was due to the generation of superoxide (O2−) radicals. In conclusion, the results of the present study suggest that CD20, CD59, and complement have a role in the in vitro cytotoxic effect of rituximab, which is mediated by a caspase-independent process that involves ROS generation.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V98.9.2771
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2001
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