Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Refractory or Relapsed Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5356-5356
Author(s):  
Hugues de Lavallade ◽  
Reda Bouabdallah ◽  
Catherine Faucher ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cumulative Incidence ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cell Group ◽  
High Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT. Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years). In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR. We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.

Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women

2001 ◽  
Vol 19 (5) ◽  
pp. 1381-1387 ◽  
Author(s):  
Rebecca A. Nelson ◽  
Alexandra M. Levine ◽  
Leslie Bernstein
Keyword(s):  
B Cell ◽  
Postmenopausal Women ◽  
Lower Risk ◽  
Hodgkin’S Lymphoma ◽  
Reproductive Factors ◽  
Hodgkin's Lymphoma ◽  
High Grade ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE: The incidence rates of non-Hodgkin’s lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.

Tumor Targeting, Dosimetry and Clinical Response Data for Lymphorad-131 (LR131; Iodine I-131 Labeled B-Lymphocyte Stimulator) in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 750-750 ◽  
Author(s):  
Andrew Belch ◽  
Alexander McEwan* ◽  
Joanne Hewitt* ◽  
Terence Riauka ◽  
Michael Stabin* ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Pet Imaging ◽  
Hodgkin’S Lymphoma ◽  
B Lymphocyte ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
B Lymphocyte Stimulator

Abstract LR131 is a novel radioconjugate consisting of B Lymphocyte Stimulator (BLyS) protein, a B cell maturation factor of the TNF family that binds selectively to immunoglobulin-positive B cells, labeled with Iodine I 131. BLyS receptors are present on normal B cells and B cell malignancies. Ten subjects with relapsed, refractory follicular non-Hodgkin’s lymphoma (8M/2F, age 33–61) have been entered on study at the Cross Cancer Institute as part of a multicenter phase 1 dose escalation trial. FDG-PET and CT imaging were performed prior to and following LR131 therapy to evaluate tumor response and recurrence. Previous therapies for these patients included single and multiagent chemotherapy, limited field external beam radiation therapy and Rituximab with/without concomitant chemotherapy. Patients had an average of 2.6 previous therapies (range 1–4). Patients received an imaging/dosimetry dose of 5–7 mCi of LR131 followed 1–2 weeks later by the therapeutic dose. CT and PET confirmed specific tumor localization in all patients. Ten of ten patients targeted sites of disease seen on CT and PET with LR131 although one patient with rapidly progressing end stage disease did not uniformly target a very large tumor mass in the abdomen/pelvis. Administered activities for therapy were 0.35 mCi/kg (10 m g/kg BLyS), 0.70 mCi/kg (30 m g/kg BLyS), 1.35 mCi/kg (75 m g/kg BLyS) and 1.70 mCi/kg (75 m g/kg BLyS) for the first four cohorts, respectively. Of 8 evaluable patients through at least 12 weeks of follow-up there were 2 CRu, 2 PR and 1 SD. In the two patients with CRu, follow-up PET scanning was negative for FDG accumulation in all areas of previous activity. One patient had significantly decreased activity on PET (4 weeks) later confirmed as PR by CT. Two patients have been retreated including one CRu (1 year) who showed renewed positive activity on PET imaging (negative CT) which returned to negative following retreatment and 1 PR. There have been no dose limiting toxicities seen to date on initial or retreatment. Time activity curves were generated after drawing ROIs and analyzed with SAAM II. Doses were calculated using MIRDOSE 3.1 (Stabin 1996). Deposited doses to critical organs were 0.48, 0.55, 2.13, 0.49, 0.37 cGy/mCi to the liver, lung, kidney, marrow and total body, respectively, and were significantly lower than those seen with the approved iodine labeled anti-CD20 monoclonal antibody (3.03, 2.92, 7.25, 2.41, 0.89 cGy/mCi for the same organs). LR131 demonstrated rapid clearance from blood and normal organs with retained activity in sites of tumor. Tumor deposited doses ranged from 45 cGy in the patient that did not target to 3600 cGy. CONCLUSION: LR131, at the administered doses studied to date, has been well tolerated with only mild to moderate reversible toxicity. LR131 has demonstrated targeting and clinical efficacy that has correlated with CT and PET imaging

Genome-Wide Analysis of B Cell Non-Hodgkin’s Lymphoma Disclosed Frequent Involvement of Genes in NFkB Pathway

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 807-807
Author(s):  
Motohiro Kato ◽  
Kumi Nakazaki ◽  
Yasuharu Sato ◽  
Kengo Takeuchi ◽  
Masashi Sanada ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
High Grade ◽  
Genome Wide Analysis ◽  
Non Hodgkin’S Lymphoma ◽  
Genome Wide ◽  
Non Hodgkin's Lymphoma ◽  
Nfkb Pathway ◽  
Homozygous Deletions

Abstract B cell non-Hodgkin’s lymphoma (B-NHL) consists of different pathological entities that are frequently characterized by distinct genetic alterations. However, the knowledge on these genetic lesions in B-NHL is still limited. In order to obtain a more comprehensive view of genetic lesions in B-NHL, we performed genome-wide analysis of copy number (CN) alterations as well as allelic imbalances using Affymetrix SNP arrays in 190 B-NHL cases, including 64 samples of diffuse large B-cell lymphoma (DLBCL), 62 of follicular lymphoma (FL), 64 of mucosa-associated lymphoid tissue lymphoma (MALT-L). SNP array data were analyzed with CNAG/AsCNAR software, which enabled sensitive detection of CN alterations in allele-specific manner, and thus allelic imbalances, without depending on availability of paired normal controls. Most frequent numerical abnormalities in B-NHL were gains of chromosomes 3 and 18, although gains of chromosome 3 were less prominent in FL. Chromosomal deletions that lead to loss of heterozygosity (LOH) were commonly found in 1p, 6q and 10q. However, the more chracteristic feature of B-NHL genomes was high frequency of CN netural LOH or uniparental disomy (UPD), which was found in 35 cases of DLBCL (55%), 32 cases of FL (52%) and 18 cases of MALT-L (28%). It is widely distributed in the genome, but more frequently found in 1p, 1q, 6p, 6q and 12q. High-grade amplifications and homozygous deletions frequently provide a clue to identify relevant gene targets. In our series, 12 loci of high-grade amplifications and 14 loci of homozygous deletions were identified, and helped to specify the candidate genes. These regions included, FCGR2B amplified in 5 cases of DLBCL, RERE amplified in 2 cases of FL and CDKN2A/CDKN2B deleted in 9 cases of DLBCL. The most notable finding in the current study was, however, the identification of common genomic alterations in genes that regulate activation of NFkB pathway in more than 50% of B-NHL cases. Eight lymphoma cases harbored high-grade amplification of cREL gene, and gain including cREL was detected in 28 samples (14.7%). Fourteen cases had gains or amplification of TRAF6, and another 16 cases had deletion at 10q including PTEN. These abnormalities were supposed to cause dysregulation of NFkB. Aberrant NFkB activity has long been implicated in the pathogenesis of B-NHL, and our study confirmed that dysregulation of NFkB pathway was main mechanism of lymphomagenesis, providing further rationale that he treatment against malignant lymphoma with inhibitor of NF kappa B pathway.

Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up

2004 ◽  
Vol 22 (23) ◽  
pp. 4711-4716 ◽  
Author(s):  
Myron S. Czuczman ◽  
Robin Weaver ◽  
Baha Alkuzweny ◽  
Judy Berlfein ◽  
Antonio J. Grillo-López
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Molecular Remission ◽  
Prior Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Long-term follow-up with updated time to disease progression (TTP) and duration of response (DR) data are presented from a multicenter, phase II trial of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma (NHL). Revised response rates based on International Workshop Response Criteria are also provided. Patients and Methods Enrollment began in April 1994 and consisted of patients with histologically confirmed, low-grade, B-cell lymphoma who had received no prior chemotherapy or who had no more than four prior standard therapies. Patients received six cycles of CHOP and six infusions of rituximab. Results Eight (21%) of the 38 treated patients were classified as International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior chemotherapy. Nine (24%) of 38 were considered poor risk according to the Follicular Lymphoma International Prognostic Index. Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. Conclusion Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.

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