Long-Term Outcome of Cyclosporin A Therapy for T-Cell Large Granular Lymphocyte Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2063-2063
Author(s):  
Attaphol Pawarode ◽  
Paul K. Wallace ◽  
Laurie A. Ford ◽  
Maurice Barcos ◽  
Maria R. Baer
Keyword(s):  
Platelet Count ◽  
T Cell ◽  
Growth Factor ◽  
Cyclosporin A ◽  
Gene Rearrangement ◽  
Large Granular Lymphocyte ◽  
Severe Neutropenia ◽  
Lgl Leukemia

Abstract T-cell large granular lymphocyte (T-LGL) leukemia is a rare indolent lymphoproliferative disorder diagnosed by presence of >2,000/μL peripheral CD3+CD8+CD16+/−CD56 +/−CD57+ LGL and/or evidence of T-LGL clonality by T-cell receptor (TCR) gene rearrangement, accompanied by neutropenia and/or other cytopenias. We reported the efficacy of cyclosporin A (CsA) in the treatment of LGL-associated neutropenia [Blood1998;91:3372–8] and we report here long-term follow-up of our larger patient (pt) cohort. Between 1982 and 2006, 18 pts were diagnosed with T-LGL leukemia with the above strict criteria (M:F 11:7; median age, 67; range, 48–84 years). Mean follow-up from diagnosis is 59 (range, 2–303) months. Autoimmune phenomena were present in 6 (33%), including pure red cell aplasia in two, lymphocytic colitis and ascites in one, and erosive osteoarthritis and pulmonary granulomatous vasculitis in one other. Splenomegaly was present in 6 (33%). Median (range) hemoglobin (Hb), absolute neutrophil count (ANC) and platelet count were 10.4 (3.6–15.5) g/dL, 1,100 (0–5,900)/μL and 152,000 (69,000–583,000)/μL. Anemia, neutropenia (ANC<1,000/μL), severe neutropenia (ANC<500/μL) and thrombocytopenia were present in 9 (50%), 13 (72%), 6 (33%), and 5 (28%), respectively. Four (22%) had one cytopenia, ten (56%) bicytopenia and one (6%) pancytopenia. Median (range) absolute number and percentage of peripheral LGL by flow cytometry were 1,147 (59–9,327)/μL and 31 (3.3–66.9) %. TCR gene rearrangement was present in 16 (89%). Fourteen pts (78%) required treatment early; median treatment-free survival was only 1.0 (95% CI, 0–8.4) months. Indications for initiation of treatment included Hb<9 g/dL, ANC<500/μL, ANC<1,000/μL with recurrent infections and platelet count<50,000/μL. CsA was initiated in 11 pts (61%). The median duration of CsA therapy was 47 (range, 4.5–186) months. Four pts were still receiving CsA at last follow-up. Four pts (40%) achieved sustained complete hematologic improvement (HI) by MD Anderson response criteria [Leuk Res 2007;31:939–45], 1 (10%) major HI and 2 minor HI (20%), resulting in an overall HI of 70%. One other (10%) had mixed HI and 2 (20%) had progressive disease. G-CSF was initiated simultaneously with, and added later to, CsA in 1 (10%) and 2 (20%) pts, respectively, and erythropoietin (Epo) in 1 (10%) and 3 (30%), respectively. The addition of growth factor resolved neutropenia and/or anemia in two additional pts, resulting in overall and complete HI of 80% and 50% respectively. Median time (range) to maximum HI with CsA, G-CSF and Epo were 2.5 (0.2–27), 0.7(0.6–1.9) and 1.5 (0.9–1.9) months, respectively. Renal insufficiency, hypertension and/or hypomagnesemia occurred in 7 (70%). CsA tapering and discontinuation were successful in two (40%) of the five pts who achieved complete HI, 91 and 186 months after initiation. Four pts (22.2%) have not required any treatment 8, 8, 33 and 80 months after diagnosis, and two received Epo and one HIV therapy alone. All except one were alive at the mean follow-up time of 59 (range, 2–303) months and median survival has not been reached. Thus T-LGL leukemia usually requires treatment early after diagnosis, but has an excellent prognosis. CsA with or without growth factor support is an effective treatment, leading to overall and complete HI in 80% and 50%, respectively. Successful tapering and discontinuation of therapy may be possible in 40% of pts who achieve long-term complete HI.

Long-term safety and efficacy of cyclosporin A therapy for T-cell large granular lymphocyte leukemia

2009 ◽  
Vol 51 (2) ◽  
pp. 338-341 ◽  
Author(s):  
Attaphol Pawarode ◽  
Paul K. Wallace ◽  
Laurie A. Ford ◽  
Maurice Barcos ◽  
Maria R. Baer
Keyword(s):  
T Cell ◽  
Cyclosporin A ◽  
Large Granular Lymphocyte ◽  
Safety And Efficacy ◽  
Large Granular Lymphocyte Leukemia

scholarly journals Neutropenia Associated With T-Cell Large Granular Lymphocyte Leukemia: Long-Term Response to Cyclosporine Therapy Despite Persistence of Abnormal Cells

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3372-3378 ◽  
Author(s):  
Raman Sood ◽  
Carleton C. Stewart ◽  
Peter D. Aplan ◽  
Hiroyuki Murai ◽  
Pamela Ward ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Large Granular Lymphocyte ◽  
Severe Neutropenia ◽  
Multiparameter Flow Cytometry ◽  
Gene Rearrangements ◽  
Aortofemoral Bypass ◽  
Blood Samples ◽  
Abnormal Cells ◽  
Lgl Leukemia

Abstract T-cell large granular lymphocyte (T-LGL) leukemia is clinically indolent, but is associated with severe neutropenia in approximately 50% of cases. The pathogenesis of the neutropenia is unclear. We report reversal of severe neutropenia associated with T-LGL leukemia in five patients treated with cyclosporine (CSA). All five had persistent neutrophil counts below 0.5 × 109/L, two had agranulocytosis, and four had recurrent infections. Increased populations of LGL were present in blood and marrow, with a T-LGL immunophenotype (CD3+CD8+CD16±CD56±CD57+) shown by multiparameter flow cytometry, and clonal T-cell receptor (TCR) gene rearrangements in two of two pretreatment blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every 12 hours, with subsequent dose adjustments based on trough serum levels. Four patients attained normal neutrophil counts with CSA alone; one required addition of low-dose granulocyte-macrophage colony-stimulating factor. Time to attainment of 1.5 × 109/L neutrophils ranged from 21 to 75 days. Attempts to taper and withdraw CSA resulted in recurrent neutropenia. Three patients have maintained normal neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two patients died 1.7 and 4.6 years after initiation of CSA despite normal neutrophil counts—one of metastatic melanoma and one of complications after aortofemoral bypass surgery. Despite resolution of neutropenia, increased populations of T-LGL cells have persisted in all patients during CSA therapy, as shown by morphology and flow cytometry and by the presence of clonal TCR gene rearrangements in four patients' posttreatment blood samples. We conclude that CSA is an effective therapy for neutropenia associated with T-LGL leukemia, and that resolution of neutropenia despite persistence of abnormal cells implies that CSA may inhibit T-LGL secretion of yet unidentified mediators of neutropenia.

Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity

2000 ◽  
Vol 65 (4) ◽  
pp. 272-275 ◽  
Author(s):  
Takayuki Saitoh ◽  
Masamitsu Karasawa ◽  
Masataka Sakuraya ◽  
Nakamura Norio ◽  
Tohma Junko ◽  
...  
Keyword(s):  
T Cell ◽  
Serum Level ◽  
Cyclosporin A ◽  
Fas Ligand ◽  
Large Granular Lymphocyte ◽  
Cell Type ◽  
Lgl Leukemia

scholarly journals Neutropenia Associated With T-Cell Large Granular Lymphocyte Leukemia: Long-Term Response to Cyclosporine Therapy Despite Persistence of Abnormal Cells

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3372-3378 ◽  
Author(s):  
Raman Sood ◽  
Carleton C. Stewart ◽  
Peter D. Aplan ◽  
Hiroyuki Murai ◽  
Pamela Ward ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Large Granular Lymphocyte ◽  
Severe Neutropenia ◽  
Multiparameter Flow Cytometry ◽  
Gene Rearrangements ◽  
Aortofemoral Bypass ◽  
Blood Samples ◽  
Abnormal Cells ◽  
Lgl Leukemia

T-cell large granular lymphocyte (T-LGL) leukemia is clinically indolent, but is associated with severe neutropenia in approximately 50% of cases. The pathogenesis of the neutropenia is unclear. We report reversal of severe neutropenia associated with T-LGL leukemia in five patients treated with cyclosporine (CSA). All five had persistent neutrophil counts below 0.5 × 109/L, two had agranulocytosis, and four had recurrent infections. Increased populations of LGL were present in blood and marrow, with a T-LGL immunophenotype (CD3+CD8+CD16±CD56±CD57+) shown by multiparameter flow cytometry, and clonal T-cell receptor (TCR) gene rearrangements in two of two pretreatment blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every 12 hours, with subsequent dose adjustments based on trough serum levels. Four patients attained normal neutrophil counts with CSA alone; one required addition of low-dose granulocyte-macrophage colony-stimulating factor. Time to attainment of 1.5 × 109/L neutrophils ranged from 21 to 75 days. Attempts to taper and withdraw CSA resulted in recurrent neutropenia. Three patients have maintained normal neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two patients died 1.7 and 4.6 years after initiation of CSA despite normal neutrophil counts—one of metastatic melanoma and one of complications after aortofemoral bypass surgery. Despite resolution of neutropenia, increased populations of T-LGL cells have persisted in all patients during CSA therapy, as shown by morphology and flow cytometry and by the presence of clonal TCR gene rearrangements in four patients' posttreatment blood samples. We conclude that CSA is an effective therapy for neutropenia associated with T-LGL leukemia, and that resolution of neutropenia despite persistence of abnormal cells implies that CSA may inhibit T-LGL secretion of yet unidentified mediators of neutropenia.

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

scholarly journals Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2352-2352
Author(s):  
Tomas Jose Gonzalez-Lopez ◽  
Fernando Fernandez-Fuertes ◽  
Maria Cristina Pascual Izquierdo ◽  
Isabel Caparros ◽  
Silvia Bernat ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Time ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Previous Treatment ◽  
Complete Response ◽  
Platelet Response ◽  
Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

scholarly journals Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1116-1119 ◽  
Author(s):  
TP Jr Loughran ◽  
T Coyle ◽  
MP Sherman ◽  
G Starkebaum ◽  
GD Ehrlich ◽  
...  
Keyword(s):  
T Cell ◽  
Large Granular Lymphocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Enzymatic Amplification ◽  
Htlv Infection ◽  
Human T Cell ◽  
Polymerase Chain ◽  
Lgl Leukemia

Abstract We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme- linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

Sign in / Sign up

Export Citation Format

Share Document