Long Term Follow-Up of Patients with Immune Thrombocytopenic Purpura (ITP) Whose Initial Response to Rituximab Lasted a Minimum of 1 Year.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 479-479 ◽  
Author(s):  
Vivek Patel ◽  
Nino Mihatov ◽  
Nichola Cooper ◽  
Roberto Stasi ◽  
Susanna Cunningham-Rundles ◽  
...  
Keyword(s):  
Platelet Count ◽  
B Cell ◽  
Treatment Algorithm ◽  
Specific Treatment ◽  
Initial Response ◽  
Chronic Itp ◽  
Duration Of Response ◽  
Long Term Follow Up

Abstract Objective: Rituximab was licensed (1997) to treat B-cell lymphomas. As a consequence of its B-cell depleting effect, Rituxmab has been widely used in autoimmune conditions including ITP. This study assessed the long term efficacy of Rituximab in patients with chronic ITP. Methods: All patients with responses lasting more than 1 year (yr) to Rituximab treatment were included in this IRB approved study to determine the duration of response to Rituximab. Forty six patients fulfilled these criteria; thus far complete data are available for 31. The median follow up (f/u) was 2 3/4 yrs. At onset of Rituximab treatment, the 31 patients had platelet counts <30 x 10 9/l, had received two or more previous ITP treatments, and 14 (44%) had undergone splenectomy. The median age and duration of ITP were 32 yrs (range 12–65) and 1 3/4 yrs respectively. The patients received Rituximab at 375 mg/m2 weekly for 4 weeks. The 15 patients for which data are not available had similar characteristics. Results: The figure outlines what happens more than one yr from Rituximab treatment for those patients whose response lasted > 1 yr. Fourteen of the 31 patients have relapsed within the f/u period giving a 5 yr response rate of 55%. Eleven of the 14 relapsers did so within 2 1/2 yrs of their first infusion whereas 14 of the 17 patients with ongoing responses had f/u > 2 1/2 yrs. The data suggest that patients whose response is > 2 1/2 yrs have a low likelihood of relapse before 5 years. While duration of ITP prior to Rituximab treatment was significantly shorter (p< 0.001) for patients responding over 3 years (median=39 weeks) than it was for those responding between 1 and 3 years (median=176 weeks), no specific duration of ITP prior to which Rituximab should be instituted was evident. None of age, sex, time to a platelet count > 30 x 109/l, and splenectomy status predicted duration of response to Rituximab. Out of the original 31 responders, there were 25 complete responses (CR: platelet count >150 x 109/l) and 6 partial responses (PR: platelet count 30–150 x 109/l). Fifteen (60%) of the CRs and 2 of the PRs (33%) remain in lasting remission (p=NS). Characteristics such as median age, duration of ITP, gender, splenectomy status, and median duration of response were similar for both PRs and CRs. Data on toxicity are less well-developed; no serious infections, malignancies, or other major toxicities were seen in this group of patients. In conclusion, several studies including our own (Cooper Brit J Haem 2004) demonstrated that approximately 1/3 of Rituximab treated patients would have a duration of response lasting > 1 yr. Among this 1/3, now with considerable additional f/u, lasting responses to Rituximab were seen in more than half. Taken together, these findings imply that responses > 2 1/2 yrs in duration would occur in approximately 1/6 of the starting population of Rituximab-treated patients with chronic ITP with little further relapse in the subsequent 2 1/2 yrs. While informing the long term response to Rituximab, this study cannot yet provide a specific treatment algorithm. Duration of Response to Rituximab in 31 Patients with Chronic ITP with a Response Greater than 1 Year Duration of Response to Rituximab in 31 Patients with Chronic ITP with a Response Greater than 1 Year

Tositumomab and I 131 Tositumomab Achieves Complete Remissions Lasting > 10 Years In Patients with Chemotherapy-Refractory Low-Grade and Transformed B-Cell Lymphomas

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3960-3960
Author(s):  
Mark S. Kaminski ◽  
Andrew D. Zelenetz ◽  
Oliver W. Press ◽  
Mansoor N. Saleh ◽  
John P. Leonard ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Response Duration ◽  
Complete Response ◽  
Median Number ◽  
Low Grade ◽  
Duration Of Response ◽  
Long Term Follow Up

Abstract Abstract 3960 Introduction: The efficacy and safety of tositumomab and iodine I 131 tositumomab (TST/I-131-TST), the Bexxar® Therapeutic Regimen, were evaluated in 60 patients (pts) with chemotherapy-refractory low-grade (LG) or transformed B-cell non-Hodgkin's lymphoma (B-NHL) who had received at least 2 chemotherapy regimens and had either not responded to (72%) or had progressed within 6 months of their last regimen (28%) (J Clin Onc 2001; 19:3918 and Blood 2004; Abstract 2631). The primary efficacy endpoint was comparison of the number of pts who had a longer duration of response to TST/I-131-TST with the number of pts with a longer duration of response to their last qualifying chemotherapy (LQC). Thirty-nine (65%) pts, including 20% who attained a complete response (CR), responded to TST/I-131-TST, compared to 17 (28%) pts, including 3% CR, after their LQC (p<0.001). Seventy-four percent of pts had a longer response duration after TST/I-131TST compared to the LQC. Four pts developed myelodysplasia (MDS), and 5 pts developed human anti-mouse antibodies (HAMA). We report final results of long term follow-up of these 60 pts. Patients and Methods: Pts were enrolled from 22 November 1996 to 06 March 1998. Pts alive at the last report date (1 March 2004) were followed for long-term safety and survival, and pts in remission at the last report date were followed for continued response. Results: Sixty pts received the dosimetric dose, and 58 of 60 pts received both the dosimetric and therapeutic doses of TST/I-131-TST. The median number of prior chemotherapies was 4 (range, 2–13). Fifty-nine of 60 (98%) pts had stage III/IV disease, 56% had bone marrow (BM) involvement, and 88% had ≥ two IPI risk factors at study entry. Thirty-six pts had LG B-NHL, 23 pts had a history of transformed B-NHL, and 1 pt had mantle cell NHL (MCL). Forty-eight (80%) pts have died, of whom 77% died due to lymphoma progression. Twelve pts were alive, and 6 pts were in CR at last follow-up. One pt withdrew consent for further follow-up but was in CR at 5.0 years, and the other 5 pts (4 LG, 1 transformed B-NHL) were in CR of ≥ 10 years' duration. The pts who continued in CR had received a median of 3 different prior chemotherapy regimens (range, 2–5), and no pts had received prior rituximab. For all 12 pts who attained CR, the median duration of response was 9.9 years (range, 0.7–11.7 years). Long-term toxicity included 7 pts who developed hypothyroidism. Secondary cancers included 1 lung adenocarincoma, 1 colon cancer, and 7 skin cancers which were reported previously. In addition, 1 developed a myeloproliferative disorder (MPD). No cases of MDS beyond the 4 previously reported were observed. Conclusion: A single course of TST/I-131-TST achieved durable remissions in chemotherapy-refractory LG and transformed B-NHL pts, with 5 of the 12 pts who achieved CR still in remission ≥ 10 years later. No additional cases of MDS were observed, but 1 pt developed a MPD since the last report. Thus, the final results of this study demonstrate that TST/I-131-TST is able to attain long-lasting durable CRs, with an acceptable toxicity profile, in a subset of pts with chemotherapy-refractory LG and transformed B-NHL. Disclosures: Kaminski: GlaxoSmithKline: Patents & Royalties, Research Funding. Zelenetz:GlaxoSmithKline: Research Funding. Press:GlaxoSmithKline: Research Funding; Spectrum Pharmaceuticals: Honoraria; Roche/Genentech: Honoraria. Saleh:GlaxoSmithKline, Novartis, Imcoline, Celgene: Honoraria, Speakers Bureau. Leonard:GlaxoSmithKline: Consultancy. Lister:GlaxoSmithKline: Chairman of Safety Monitoring Board for GSK. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Consultancy, Employment. Vleisides:GlaxoSmithKline: Employment. Knox:GlaxoSmithKline: Research Funding. Wahl:GlaxoSmithKline: Consultancy, Patents & Royalties; Nihon Medi Physics: Consultancy; Spectrum Pharmaceuticals: Consultancy; Naviscan PET systems: Consultancy; Threshold Pharmaceuticals: Equity Ownership. Vose:GlaxoSmithKline: Research Funding.

scholarly journals Hairy B-cell lymphoproliferative disorder and its differential diagnosis: a case with long-term follow-up

2017 ◽  
Vol 9 (1) ◽  
pp. e2017054
Author(s):  
Kensuke Matsuda ◽  
Yosuke Matsumoto ◽  
Mihiko Yoshida ◽  
Kazuho Shimura ◽  
Hiroto Kaneko ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
B Cell ◽  
Lymphoproliferative Disorder ◽  
Japanese Patient ◽  
Accurate Diagnosis ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Long Term Follow Up

Hairy B-cell lymphoproliferative disorder (HBLD) is one of chronic polyclonal B-cell lymphocytosis. We report a 47-year-old female Japanese patient diagnosed as having HBLD based on lymphocytosis with hairy cell appearance and characteristic phenotypes including CD11c+, and without B-cell monoclonalities. She was a non-smoker, and possessed HLA-DR4. She has been closely followed up without treatment and lymphoma development for over five years. Although this disease is quite rare and has been reported, to our knowledge, in only 13 Japanese cases, an accurate diagnosis, particularly differential diagnosis from persistent polyclonal B-cell lymphocytosis or hairy cell leukemia-Japanese variant is essential for the prevention of unnecessary treatments.

Reconstitution of the T Cell Repertoire Following Treatment with Alemtuzumab in Patients with B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2986-2986
Author(s):  
Mohammad R. Rezvany ◽  
Mahmood J. Tehrani ◽  
Claes Karlsson ◽  
Jeanette Lundin ◽  
Hodjattallah Rabbani ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Long Term Follow Up

Abstract Background and Methods: B-cell chronic lymphocytic leukemia (B-CLL) occurs as a result of clonal accumulation of functionally abnormal B cells. Alemtuzumab is a humanized monoclonal antibody specific for the CD52 antigen, which is highly expressed on both B-CLL cells and normal lymphocytes, but not on hematopoietic (CD34) stem cells. Alemtuzumab has been shown to effectively deplete the blood and bone marrow of lymphocytes, including CD4 and CD8 T cells, which may lead to profound immunosuppression and make patients more susceptible to infections. We and others have previously shown that the CD4 T cells in B-CLL patients may be clonally distinct from the normal population in that they present a more clonal pattern of the T-cell receptor (TCR) repertoire (Rezvany et al, Blood2003;101:1063–1070). It is therefore of interest to study the T cell repertoire following alemtuzumab administration as well as factors affecting T cell reconstitution following CD52 targeted therapy. In this study, we evaluated in depth the T-cell receptor-beta-variable sequence (TCR BV) in CD4 and CD8 T cells by real-time PCR, before and repeatedly after/during long term follow-up, in 5 B-CLL patients who had received alemtuzumab as first-line therapy (Lundin et al, Blood2002;100:768–773). Also, an analysis was conducted of CDR3 length polymorphism to describe changes in the clonality pattern. Results: A decline in most of BV genes either in CD4 or CD8 T cells was observed shortly after alemtuzumab treatment, which was followed by a gradual increase in most of the BV genes during long-term follow up. CDR3 length polymorphism analysis shortly after treatment revealed an even more highly restricted pattern in CD4 T cells compared to baseline with a shift towards a monoclonal/oligoclonal pattern regardless of increased or decreased BV usage. Furthermore, in the analysis of the clonal spectrum that was expressed shortly after alemtuzumab therapy, the number of peaks was significantly reduced in CD4 (P &lt;0.01) but not in CD8 T cells, which was followed by a gradual increase in diversity towards a polyclonal repertoire during long-term follow up. Conclusions: These results indicate that perturbations in the T cell repertoire following alemtuzumab are complex, and are not reflected by changes in CD4/CD8 T cell numbers only. The restricted CDR3 pattern present prior to therapy became even more restricted after end of treatment, followed by a normalization of CDR3 patterns in CD4 T-cells during long-term follow-up. These results further suggest a regulatory role for T cells in relation to the malignant B cell clone in patients with B-CLL.

Long-term outcomes in adults with chronic ITP after splenectomy failure

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 956-960 ◽  
Author(s):  
Robert McMillan ◽  
Carol Durette
Keyword(s):  
Platelet Count ◽  
Autoimmune Disorder ◽  
Corticosteroid Treatment ◽  
Long Term Outcomes ◽  
Normal Platelet ◽  
Resistant Disease ◽  
Long Term Follow Up ◽  
Additional Therapy

AbstractAdult chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder manifested by thrombocytopenia from the effects of antiplatelet autoantibodies and T lymphocyte–mediated platelet cytotoxicity. Multiple studies show that corticosteroid treatment and splenectomy, alone or together, increase platelet counts to safe levels in 60% to 70% of patients. However, there is little information on the outcomes of ITP patients refractory to splenectomy. We studied 114 patients with ITP for whom splenectomy failed and who required additional therapy; long-term follow-up was available on 105 (92%) patients. Seventy-five (71.4%) patients attained stable partial (platelet count greater than 30 × 109/L) or complete (normal platelet count) remission; 51 patients remained in remission after therapy was discontinued, whereas 24 patients required continued treatment. Median time to remission after splenectomy failure was 46 months (range, 1-437 months). Median remission durations were 60 months (range, 10-212 months) for patients off therapy and 48 months (range, 2-167 months) for patients on therapy. Thirty (29.6%) patients remained unresponsive to treatment. Thirty-two patients died, 17 (15.7%) of ITP (bleeding, 11 patients; therapy complications, 6 patients) and 15 (13.9%) of unrelated causes. We conclude that most patients with refractory ITP attain stable remission, though on average this occurs slowly. However, a subpopulation with severe, resistant disease experiences significant morbidity and mortality.

scholarly journals B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response

2007 ◽  
Vol 66 (9) ◽  
pp. 1259-1262 ◽  
Author(s):  
K. P Ng ◽  
G. Cambridge ◽  
M. J Leandro ◽  
J. C W Edwards ◽  
M. Ehrenstein ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Systemic Lupus ◽  
Predictors Of Response ◽  
Long Term Follow Up
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