26 results
Search Results
2. A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma.
- Author
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Armand, Philippe, Redd, Robert, Bsat, Jad, Mayuram, Sangeetha, Giardino, Angela, Fisher, David C., LaCasce, Ann S., Jacobson, Caron, Davids, Matthew S., Brown, Jennifer R., Weng, Li, Wilkins, Jennifer, Faham, Malek, Freedman, Arnold S., Joyce, Robin, and Jacobsen, Eric D.
- Subjects
RITUXIMAB ,CYTARABINE ,MANTLE cell lymphoma ,STEM cell transplantation ,DISEASE progression ,CYCLOPHOSPHAMIDE ,THERAPEUTICS - Abstract
Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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3. Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma.
- Author
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Khashab, Tamer, Hagemeister, Fredrick, Romaguera, Jorge E., Fanale, Michelle A., Pro, Barbara, McLaughlin, Peter, Rodriguez, M. Alma, Neelapu, Sattva S., Fayad, Luis, Younes, Anas, Feng, Lei, Vega, Francisco, Kwak, Larry W., and Samaniego, Felipe
- Subjects
PROGRESSION-free survival ,BONE marrow ,THERAPEUTICS ,MYELODYSPLASTIC syndromes ,FOLLOW-up studies (Medicine) - Abstract
Summary: In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well‐tolerated in previously untreated patients with advanced‐stage, indolent non‐Hodgkin lymphoma (iNHL). After a median patient follow‐up of more than 108 months, we performed an intent‐to‐treat analysis of our 83 participants. Progression‐free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten‐year PFS rates for those with beta‐2‐microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10‐year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long‐term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10‐year follow‐up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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4. The absolute percent deviation of IGHV mutation rather than a 98% cut-off predicts survival of chronic lymphocytic leukaemia patients treated with fludarabine, cyclophosphamide and rituximab.
- Author
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Jain, Preetesh, Nogueras González, Graciela M., Kanagal‐Shamanna, Rashmi, Rozovski, Uri, Sarwari, Nawid, Tam, Constantine, Wierda, William G., Thompson, Philip A., Jain, Nitin, Luthra, Rajyalakshmi, Quesada, Andres, Sanchez‐Petitto, Gabriela, Ferrajoli, Alessandra, Burger, Jan, Kantarjian, Hagop, Cortes, Jorge, O'Brien, Susan, Keating, Michael J., and Estrov, Zeev
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GENETIC mutation ,IMMUNOGLOBULIN heavy chains ,GERM cells ,CHRONIC lymphocytic leukemia ,FLUDARABINE ,CYCLOPHOSPHAMIDE ,RITUXIMAB ,PROGNOSIS ,THERAPEUTICS - Abstract
The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline ( IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia ( CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab ( FCR) trial with a median of 10 years follow-up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression-free ( PFS) and overall survival ( OS) ( P < 0·001). Furthermore, we validated this finding in 323 patients treated with FCR off-protocol and in the total cohort ( n = 535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR-treated cohorts ( P < 0·001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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5. Dose adjusted- EPOCH-R and mediastinal disease may improve outcomes for patients with gray-zone lymphoma.
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Chihara, Dai, Westin, Jason R., Miranda, Roberto N., Cheah, Chan Y., Oki, Yasuhiro, Turturro, Francesco, Romaguera, Jorge E., Neelapu, Sattva S., Nastoupil, Lorreta J., Fayad, Luis E., Rodriguez, M. Alma, Fowler, Nathan H., Orlowski, Robert Z., Wang, Michael, Hagemeister, Fredrick B., Medeiros, L. Jeffrey, and Fanale, Michelle A.
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LYMPHOMAS ,ETOPOSIDE ,CYCLOPHOSPHAMIDE ,DOXORUBICIN ,VINCRISTINE ,PREDNISONE ,RITUXIMAB ,PATIENTS ,THERAPEUTICS - Abstract
The article presents a study which analyzed patients diagnosed with gray-zone lymphoma (GZL) at the University of Texas MD Anderson Cancer Center in Houston, Texas. Topics discussed include characteristics of patients with GZL, longer progression-free survival (PFS) found in patients with mediastinal GZL, and indication that dose-adjusted etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (DA-EPOCH-R) may improve outcome for patients with GZL.
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- 2017
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6. Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.
- Author
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Paludo, Jonas, Abeykoon, Jithma P., Kumar, Shaji, Shreders, Amanda, Ailawadhi, Sikander, Gertz, Morie A., Kourelis, Taxiarchis, King, Rebecca L., Reeder, Craig B., Leung, Nelson, Kyle, Robert A., Buadi, Francis K., Habermann, Thomas M., Dingli, David, Witzig, Thomas E., Dispenzieri, Angela, Lacy, Martha Q., Go, Ronald S., Lin, Yi, and Gonsalves, Wilson I.
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DEXAMETHASONE ,RITUXIMAB ,CYCLOPHOSPHAMIDE ,WALDENSTROM'S macroglobulinemia ,DISEASE relapse ,NEUTROPENIA ,THROMBOCYTOPENIA ,PATIENTS ,THERAPEUTICS - Abstract
The management of Waldenström macroglobulinaemia ( WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide ( DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88
WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate ( ORR) was 87%. The median progression-free survival ( PFS) and time-to-next-therapy ( TTNT) were 32 (95% confidence interval [ CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort ( n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [ NR]) and NR (95% CI: 37- NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P . The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. [ABSTRACT FROM AUTHOR]- Published
- 2017
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7. State of the art - how I manage immune thrombocytopenia.
- Author
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Cooper, Nichola
- Subjects
IDIOPATHIC thrombocytopenic purpura ,DISEASE progression ,INTRAVENOUS immunoglobulins ,RITUXIMAB ,IMMUNOSUPPRESSIVE agents ,PATIENTS ,THERAPEUTICS - Abstract
The management of patients with immune thrombocytopenia ( ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins ( IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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8. Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.
- Author
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Shankar, Ananth G., Roques, Gaelle, Kirkwood, Amy A., Lambilliotte, Anne, Freund, Katja, Leblanc, Thierry, Hayward, Janis, Abbou, Samuel, Ramsay, Alan D., Schmitt, Claudine, Gorde‐Grosjean, Stephanie, Pacquement, Hélène, Haouy, Stephanie, Boudjemaa, Sabah, Aladjidi, Nathalie, Hall, Georgina W., and Landman‐Parker, Judith
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HODGKIN'S disease in children ,RITUXIMAB ,CANCER chemotherapy ,DISEASE remission ,DISEASE progression ,THERAPEUTICS - Abstract
Advanced stage nodular lymphocyte predominant Hodgkin lymphoma ( nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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9. The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab.
- Author
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Forero‐Castro, Maribel, Robledo, Cristina, Lumbreras, Eva, Benito, Rocio, Hernández‐Sánchez, Jesús M., Hernández‐Sánchez, María, García, Juan L., Corchete‐Sánchez, Luis A., Tormo, Mar, Barba, Pere, Menárguez, Javier, Ribera, Jordi, Grande, Carlos, Escoda, Lourdes, Olivier, Carmen, Carrillo, Estrella, García de Coca, Alfonso, Ribera, Josep‐María, and Hernández‐Rivas, Jesús M.
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BURKITT'S lymphoma ,CANCER chemotherapy ,RITUXIMAB ,NUCLEOTIDE sequencing ,GENETIC mutation ,HEALTH outcome assessment ,THERAPEUTICS - Abstract
The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma ( BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization ( CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing ( NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy ( P = 0·038), shorter progression-free survival ( PFS; P = 0·007) and overall survival ( OS; P = 0·009). The integrative analysis of array- CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS ( P = 0·011) while TCF3 alterations were associated with shorter OS ( P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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10. Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center.
- Author
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Chihara, Dai, Cheah, Chan Y., Westin, Jason R., Fayad, Luis E., Rodriguez, Maria A., Hagemeister, Fredrick B., Pro, Barbara, McLaughlin, Peter, Younes, Anas, Samaniego, Felipe, Goy, Andre, Cabanillas, Fernando, Kantarjian, Hagop, Kwak, Larry W., Wang, Michael L., and Romaguera, Jorge E.
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MANTLE cell lymphoma ,RITUXIMAB ,CYCLOPHOSPHAMIDE ,VINCRISTINE ,DOXORUBICIN ,DEXAMETHASONE ,CYTARABINE ,CANCER chemotherapy ,THERAPEUTICS - Abstract
Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years). [ABSTRACT FROM AUTHOR]
- Published
- 2016
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11. An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy.
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Sarid, Nadav, Ahmad, Humayun N, Wotherspoon, Andrew, Dearden, Claire E, Else, Monica, and Catovsky, Daniel
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LEUKEMIA diagnosis ,LEUKEMIA genetics ,HYPERSPLENISM ,RITUXIMAB ,DISEASE relapse ,ELASTICITY ,DIAGNOSIS ,THERAPEUTICS - Abstract
We describe three cases of relapsed hairy cell leukaemia (HCL) treated with pentostatin plus rituximab. All three achieved bone marrow complete remission but had persistent splenomegaly and hypersplenism. Because of the clinical uncertainty of its significance, they were all splenectomized. The spleen histology showed no evidence of HCL, but a five-fold thickening of the splenic capsule and areas of fibrosis in the red pulp. This process may have contributed to the lack of elasticity and caused the persistent splenomegaly. We discuss the clinical implications for future patient management. The three patients remain in remission at 1 +, 5 + and 9 + years. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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12. Lack of effectiveness of routine clinic and blood test‐based follow‐up for diffuse large B cell lymphoma.
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Chasty, Beth, Patterson, Michael, Murray, Louise J., Johnson, Rod, Thomas, Emma, Gilson, Di, Burton, Cathy, and Prestwich, Robin J. D.
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DIFFUSE large B-cell lymphomas ,RITUXIMAB ,BLOOD testing ,DISEASE relapse ,LACTATE dehydrogenase ,THERAPEUTICS - Abstract
The article discusses a study which evaluated the approach a surveillance following remission with first line therapy for diffuse large B cell lymphoma (DLBCL) in the rituximab era with clinical follow-up for at least 5 years with routine blood tests, including lactate dehydrogenase (LDH), without routine imaging. Topics covered include patient and treatment characteristics, the pattern of relapse detection, and the utility of routine blood tests to detect relapse.
- Published
- 2018
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13. Prognostic model for mantle cell lymphoma in the rituximab era: a nationwide study in Japan.
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Chihara, Dai, Asano, Naoko, Ohmachi, Ken, Kinoshita, Tomohiro, Okamoto, Masataka, Maeda, Yoshinobu, Mizuno, Ishikazu, Matsue, Kosei, Uchida, Toshiki, Nagai, Hirokazu, Nishikori, Momoko, Nakamura, Shigeo, Ogura, Michinori, and Suzuki, Ritsuro
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MANTLE cell lymphoma ,LYMPHOMAS ,LYMPHOMA risk factors ,RITUXIMAB ,CANCER chemotherapy ,MULTIVARIATE analysis ,THERAPEUTICS ,PROGNOSIS - Abstract
Mantle cell lymphoma ( MCL) is essentially incurable with conventional chemotherapy. The MCL International Prognostic Index ( MIPI) is a validated specific prognostic index, but was derived from patients with advanced-stage disease primarily in the pre-rituximab era. We analysed 501 MCL patients (median age, 67 years; range 22-90) treated with rituximab-containing chemotherapy, and evaluated the prognostic factors adjusted by the treatment. Five-year overall survival ( OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%, respectively. Additional to MIPI risk factors, multivariate analysis revealed that low serum albumin and bone-marrow involvement were also significantly associated with a poor outcome. The revised- MIPI (R- MIPI) was constructed using six factors, namely age, performance status, white blood cell count, serum lactate dehydrogenase, bone-marrow involvement and serum albumin, which is divided into four prognostic groups. Five-year OS in low, low-intermediate (L-I), high-intermediate (H-I) and high R- MIPI groups was 92%, 75%, 61% and 19%, respectively. Hazard ratio for OS of L-I, H-I and high risk to low risk patients were 5·4, 8·3 and 33·0, respectively. R- MIPI, a new prognostic index with easy application to the general patient population, shows promise for identifying low- and high-risk MCL patients in the rituximab era. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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14. Prognostic value of complete remission status at end-oftreatment FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: systematic review and meta-analysis.
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Adams, Hugo J. A., Nievelstein, Rutger A. J., and Kwee, Thomas C.
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POSITRON emission tomography ,B cell lymphoma ,RITUXIMAB ,CYCLOPHOSPHAMIDE ,DOXORUBICIN ,VINCRISTINE ,MEDLINE ,DISEASE remission ,THERAPEUTICS - Abstract
This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The systematic Pub- Med/MEDLINE search yielded seven suitable studies comprising a total of 737 R-CHOP-treated DLBCL patients who were in complete remission at end-of-treatment FDG-PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end-of-treatment FDG-PET ranged from 7.0% to 20%, with a weighted summary proportion of 13.7%. Five of seven studies reported progression-free survival (PFS) of these patients at various specific time points, i.e., 2-year PFS (n = 1), estimated 3-year PFS (n = 3) and 5-year PFS (n = 1), which was 83%, 85-86.4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3-year OS (n = 2) and estimated 5-year OS (n = 1), which were 90%, 93.6% and 83%, respectively. In conclusion, a non-negligible proportion of R-CHOP-treated DLBCL patients who achieve complete remission according to end-of-treatment FDG-PET experiences disease relapse during follow- up. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
15. Response-adapted therapy for aggressive non-Hodgkin's lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404).
- Author
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Swinnen, Lode J., Li, Hailun, Quon, Andrew, Gascoyne, Randy, Hong, Fangxin, Ranheim, Erik A., Habermann, Thomas M., Kahl, Brad S., Horning, Sandra J., and Advani, Ranjana H.
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DIFFUSE large B-cell lymphomas ,PROGRESSION-free survival ,RITUXIMAB ,IFOSFAMIDE ,CARBOPLATIN ,ETOPOSIDE ,POSITRON emission tomography ,CYCLOPHOSPHAMIDE ,THERAPEUTICS - Abstract
A persistently positive positron emission tomography ( PET) scan during therapy for diffuse large B-cell lymphoma ( DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R- ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R- ICE, PET-negative patients received two more cycles of R- CHOP. A ≥45% 2-year progression-free survival ( PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival ( OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R- ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
16. Four doses of unpegylated versus one dose of pegylated filgrastim as supportive therapy in R- CHOP-14 for elderly patients with diffuse large B-cell lymphoma.
- Author
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Bozzoli, Valentina, Tisi, Maria C., Maiolo, Elena, Alma, Eleonora, Bellesi, Silvia, D'Alo’, Francesco, Voso, Maria T., Leone, Giuseppe, and Hohaus, Stefan
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FILGRASTIM ,RITUXIMAB ,CYCLOPHOSPHAMIDE ,LYMPHOMA treatment ,DOXORUBICIN ,THERAPEUTICS - Abstract
The primary objective of this prospective, randomized study was to compare the efficacy of a reduced regimen of only four doses of unpegylated filgrastim from day +8 to +11 per cycle with a standard once per cycle administration of pegylated filgrastim to maintain dose-intensity of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone given every 14 d) in previously untreated elderly patients with diffuse large B-cell lymphoma ( DLBCL). We included 51 patients (median age 66 years, range 60-76). Median dose intensity did not differ between the group of 24 patients receiving four doses of unpegylated filgrastim of each cycle (87·5%) and the group of 27 patients receiving pegylated filgrastim once per cycle on day 2 (89·4%) ( P = 0·9). There was also no difference in the frequency of adverse events, such as episodes of neutropenic fever and unplanned hospitalizations. Patient characteristics that negatively influenced dose intensity were reduced performance status, advanced stage disease and poor-risk International Prognostic Index, with Eastern Cooperative Oncology Group performance status ≥2 being the most significant factor. In conclusion, a limited support with 4 d of filgrastim appears to be equivalent to pegylated filgrastim administered once per cycle, and appears to be sufficient to maintain dose-intensity of the R-CHOP-14 regimen in elderly patients with DLBCL without risk factors. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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17. Entinostat, a novel histone deacetylase inhibitor is active in B-cell lymphoma and enhances the anti-tumour activity of rituximab and chemotherapy agents.
- Author
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Frys, Sarah, Simons, Zachary, Hu, Qiang, Barth, Matthew J., Gu, Juan J., Mavis, Cory, Skitzki, Joseph, Song, Liu, Czuczman, Myron S., and Hernandez‐Ilizaliturri, Francisco J.
- Subjects
LYMPHOMA treatment ,HISTONE deacetylase inhibitors ,ANTINEOPLASTIC agents ,RITUXIMAB ,CANCER chemotherapy ,THERAPEUTICS - Abstract
Histone deacetylases ( HDACs) inhibitors are active in T-cell lymphoma and are undergoing pre-clinical and clinical testing in other neoplasms. Entinostat is an orally bioavailable class I HDAC inhibitor with a long half-life, which is under evaluation in haematological and solid tumour malignancies. To define the activity and biological effects of entinostat in B-cell lymphoma we studied its anti-tumour activity in several rituximab-sensitive or -resistant pre-clinical models. We demonstrated that entinostat is active in rituximab-sensitive cell lines ( RSCL), rituximab-resistant cell lines ( RRCL) and primary tumour cells isolated from lymphoma patients ( n = 36). Entinostat exposure decreased Bcl- XL ( BCL2L1) levels and induced apoptosis in cells. In RSCL and RRCL, entinostat induced p21 ( CDKN1A) expression leading to G1 cell cycle arrest and exhibited additive effects when combined with bortezomib or cytarabine. Caspase inhibition diminished entinostat activity in some primary tumour cells suggesting that entinostat has dual mechanisms-of-action. In addition, entinostat increased the expression of CD20 and adhesion molecules. Perhaps related to these effects, we observed a synergistic activity between entinostat and rituximab in a lymphoma-bearing severe combined immunodeficiency ( SCID) mouse model. Our data suggests that entinostat is an active HDAC inhibitor that potentiates rituximab activity in vivo and supports its further clinical development in B-cell lymphoma. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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18. Managing the challenge of PTLD in liver and bowel transplant recipients.
- Author
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Lauro, Augusto, Arpinati, Mario, and Pinna, Antonio D.
- Subjects
LYMPHOPROLIFERATIVE disorders ,LIVER transplantation ,SURGICAL complications ,IMMUNOSUPPRESSIVE agents ,MONOCLONAL antibodies ,PATIENTS ,THERAPEUTICS - Abstract
Post-transplant lymphoproliferative disorder ( PTLD) remains a common complication of liver and bowel transplantion. The ubiquity of Epstein-Barr virus ( EBV) combined with engraftment of organs rich with lymphatic tissue and the requirement of highly immunosuppressive regimens are factors that account for the high frequency and poor prognosis of PTLD in this population. Early detection of the virus followed by pre-emptive reduction of immunosuppression are essential components in the management of PTLD, but can increase the risk of graft loss. More recently, the anti-CD20 monoclonal antibody (rituximab) has been shown to improve survival in various transplant populations with PTLD, while other therapeutic options, such as chemotherapy, surgery or radiotherapy, have minimal clinical impact. EBV-directed cytotoxic T cells have shown promise in the management of PTLD but clinical use is currently limited by lack of technical facilities worldwide. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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19. A modified scoring of the NCCN- IPI is more accurate in the elderly and is improved by albumin and β2-microglobulin.
- Author
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Melchardt, Thomas, Troppan, Katharina, Weiss, Lukas, Hufnagl, Clemens, Neureiter, Daniel, Tränkenschuh, Wolfgang, Hopfinger, Georg, Magnes, Teresa, Deutsch, Alexander, Neumeister, Peter, Hackl, Hubert, Greil, Richard, Pichler, Martin, and Egle, Alexander
- Subjects
LACTATE dehydrogenase ,RITUXIMAB ,ALBUMINS ,MICROGLOBULINS ,COHORT analysis ,THERAPEUTICS - Abstract
The International Prognostic Index ( IPI) has been used for decades in diffuse large B-cell lymphoma ( DLBCL). A retrospective cancer registry analysis in North America showed significantly improved results when an enhanced IPI, the National Comprehensive Cancer Network ( NCCN)- IPI was applied. This novel score puts more weight on age and high levels of lactate dehydrogenase ( LDH). Nevertheless, it remains unclear if these results can be extrapolated to the general population. This retrospective bi-centre analysis included 499 unselected DLBCL patients who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and 2013. In our cohort, the NCCN- IPI was more accurate in identifying patients at low or high risk, despite older age, and more patients with increased LDH. Nevertheless, a modified scoring of the risk factors was required to more accurately identify elderly patients with a very favourable diagnosis, suggesting an impaired value of the original NCCN- IPI in the elderly. Serum β
2 -microglobulin and albumin were retained as independent prognostic factors for survival in a multivariate analysis. Our data confirm, for the first time, the superior prognostic power of the NCCN- IPI in an unselected, middle-European cohort. We furthermore propose a modified NCCN- IPI for more accurate prognostication in the elderly. Albumin and β2 -microglobulin levels are likely to add significant information to the NCCN- IPI. [ABSTRACT FROM AUTHOR]- Published
- 2015
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20. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non- Hodgkin lymphoma.
- Author
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Westin, Jason R., McLaughlin, Peter, Romaguera, Jorge, Hagemeister, Fredrick B., Pro, Barbara, Dang, Nam H., Samaniego, Felipe, Rodriguez, Maria A., Fayad, Luis, Oki, Yasuhiro, Fanale, Michelle, Fowler, Nathan, Nastoupil, Loretta, Feng, Lei, Loyer, Evelyn, and Younes, Anas
- Subjects
LYMPHOMA treatment ,PACLITAXEL ,TOPOTECAN ,RITUXIMAB ,B cell lymphoma ,SALVAGE therapy ,THERAPEUTICS ,TUMOR treatment - Abstract
Relapsed aggressive lymphomas are often treated with platinum-based chemotherapy ( PBC) followed by an autologous stem cell transplant ( ASCT). Response rates to PBC in patients with relapsed aggressive lymphomas are c. 60%, and non-responders have a dismal prognosis. Novel therapies for aggressive lymphomas, including those failing PBC, are needed. We performed a phase II study of paclitaxel, topotecan and rituximab ( TTR) in patients with relapsed or refractory diffuse large B-cell, follicular grade IIIB, or transformed lymphomas, including those who previously failed PBC. The median age of the 72 patients enrolled was 54 years. Responding patients were offered ASCT after two courses. The overall response rate was 69% for all patients ( n = 49/71) and 45% for those who previously failed PBC ( n = 9/20). With a median follow up of 125 months for the censored observations, the overall survival ( OS) and progression-free survival at 5 years was 39% and 27%, respectively. Responding patients who received ASCT had an OS of 63% at 5 years. Our results demonstrate that TTR is an effective salvage regimen for patients with relapsed aggressive B-cell lymphomas, including those who previously failed PBC. Given the declining therapeutic outcomes of salvage PBC in the rituximab era, further evaluation of TTR is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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21. Peripheral blood involvement in patients with follicular lymphoma: a rare disease manifestation associated with poor prognosis.
- Author
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Sarkozy, Clémentine, Baseggio, Lucile, Feugier, Pierre, Callet‐Bauchu, Evelyne, Karlin, Lionel, Seymour, John F., Lebras, Laure, Michallet, Anne‐Sophie, Offner, Fritz, Dumas, Olivier, Traverse‐Glehen, Alexandra, Ffrench, Martine, Lopez‐Guillermo, Armando, Berger, Françoise, Coiffier, Bertrand, Felman, Pascale, and Salles, Gilles
- Subjects
LYMPHOMAS ,LEUKEMIA diagnosis ,RITUXIMAB ,THERAPEUTICS ,CANCER patients ,PROGNOSIS ,SURVIVAL ,HODGKIN'S disease - Abstract
Follicular Lymphoma ( FL) is the second most common non-Hodgkin lymphoma ( NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase ( FL- LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL- LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL- LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL- LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index ( FLIPI) score, age and treatment. Presence of FL- LP was associated with shorter progression-free survival ( PFS) and overall survival ( OS) ( P = 0·004 and P = 0·031, respectively). Presence of FL- LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression ( TTP). A number of circulating lymphoma cells ( CLC) >4 × 10
9 /l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL- LP on TTP was validated in the PRIMA cohort ( P = 0·0004). In conclusion, FL- LP is a rare event associated with shorter PFS and patients with CLC >4 × 109 /l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options. [ABSTRACT FROM AUTHOR]- Published
- 2014
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22. Remission induction therapy containing rituximab markedly improved the outcome of untreated mature B cell lymphoma.
- Author
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Nagai, Hirokazu, Yano, Takahiro, Watanabe, Tomoyuki, Uike, Naokuni, Okamura, Seiichi, Hanada, Shuichi, Kawano, Fumio, Sunami, Kazutaka, Inoue, Nobumasa, Sawamura, Morio, Nishiura, Tetsuo, Hotta, Tomomitsu, and Horibe, Keizo
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CLINICAL trials ,RITUXIMAB ,B cells ,LYMPHOMAS ,THERAPEUTICS ,CLINICAL medicine - Abstract
Many controlled clinical trials have proven that rituximab improves the clinical outcome of patients with mature B cell lymphoma. This study was conducted to assess the contribution of rituximab in the actual clinical practice. Patients with newly diagnosed mature B cell lymphoma treated at 20 National Hospital Organization hospitals from January 2000 to December 2004 were consecutively registered. Rituximab was approved in September 2002 for indolent B cell lymphoma and in September 2003 for aggressive B cell lymphoma in Japan. The patients were divided into two groups depending on whether they received induction therapy containing rituximab. The endpoint was to evaluate the rituximab benefit based on 2-year progression-free survival (PFS) and 2-year overall survival (OS). A total 1126 patients received chemotherapies. Of these, 762 were diagnosed as diffuse large B cell lymphoma (DLBCL) and 215 as follicular lymphoma (FL). PFS and OS were markedly improved in the rituximab group compared with the non-rituximab group in patients with DLBCL (both P < 0·001) and in patients with FL ( P < 0·001 and P = 0·003 respectively). Rituximab, when used for remission induction therapy, significantly improved the clinical outcome of the mature B cell lymphoma patient in actual clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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23. Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma.
- Author
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Pro, Barbara, Leber, Brian, Smith, Mitchell, Fayad, Luis, Romaguera, Jorge, Hagemeister, Fredrick, Rodriguez, Alma, McLaughlin, Peter, Samaniego, Felipe, Zwiebel, James, Lopez, Adriana, Kwak, Larry, and Younes, Anas
- Subjects
THERAPEUTIC use of oligonucleotides ,LYMPHOMA treatment ,RITUXIMAB ,SODIUM ,STEM cell transplantation ,THERAPEUTICS - Abstract
Oblimersen sodium plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) patients. Oblimersen was administered as a continuous intravenous infusion at a daily dose of 3 mg/kg/d for 7 d on alternate weeks for 3 weeks. Rituximab was given at a weekly dose of 375 mg/m
2 for six doses. Patients with stable disease or objective response were allowed to receive a second course of treatment. The overall response rate (ORR) was 42% with 10 complete responses (CR) and eight partial responses (PR). Twelve (28%) patients achieved a minimal response or stable disease. Among the 20 patients with follicular lymphoma the ORR was 60% (eight CR, four PR). Three of the responders were refractory to prior treatment with rituximab, and two of the responses occurred in patients who had failed an autologous stem cell transplant. Median duration of response was 12 months. Most toxicities were low grade and reversible. In conclusion, oblimersen sodium can be safely combined with rituximab. The combination appears to be most beneficial in patients with indolent NHL and warrants further investigation in a large randomized trial. [ABSTRACT FROM AUTHOR]- Published
- 2008
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24. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial.
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Ribera, Josep-Maria, Oriol, Albert, Morgades, Mireia, González-Barca, Eva, Miralles, Pilar, López-Guillermo, Armando, Gardella, Santiago, López, Andres, Abella, Eugenia, and García, Marta
- Subjects
DRUG therapy ,THERAPEUTICS ,HIV ,HIV-positive persons ,PROGNOSIS - Abstract
Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 ( n = 26), 2 ( n = 19), 3 ( n = 20) and 4 or 5 ( n = 16), and median CD4 lymphocyte count of 0·158 × 10
9 /l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART. [ABSTRACT FROM AUTHOR]- Published
- 2008
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25. The significance of serum immunoglobulin paraprotein in diffuse large B‐cell lymphoma.
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Cox, M. Christina, Di Napoli, Arianna, Fabbri, Alberto, Cencini, Emanuele, and Ruco, Luigi
- Subjects
SEROTHERAPY ,DIFFUSE large B-cell lymphomas ,RITUXIMAB ,THERAPEUTICS - Published
- 2018
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26. Childhood refractory autoimmune haemolytic anaemia: Is there a role for anti-CD20 therapy (rituximab)?
- Author
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Mc Mahon, C, Babu, L, Hodgson, A, Hayat, A, Connell, N. O, and Smith, O. P
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AUTOIMMUNE hemolytic anemia ,ANEMIA in children ,CD antigens ,THERAPEUTICS - Abstract
Reports on the case of a pediatric patient with relapsed refractory autoimmune hemolytic anemia. Medical history of the patient; Outcome of treatments with rituximab or anti-CD20 antigen therapy; Recommendation to prevent opportunistic infections.
- Published
- 2002
- Full Text
- View/download PDF
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