A Retrospective Study of 67 Inflammatory Waldenström's Macroglobulinemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Dikelele Elessa ◽  
Stephanie Harel ◽  
Alexis Talbot ◽  
Marion Malphettes ◽  
Catherine Thieblemont ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Biological Characteristics ◽  
Response To Treatment ◽  
Front Line ◽  
Waldenström’S Macroglobulinemia ◽  
Line Therapy ◽  
Hematological Response ◽  
Inflammatory Syndrome ◽  
Waldenström's Macroglobulinemia

Introduction Waldenström's macroglobulinemia (WM) is an indolent lymphoma with medullary infiltration by a lymphoplasmacytic clone associated with an immunoglobulin M paraprotein. Some patients diagnosed with WM present a concomitant inflammatory syndrome: increased C-reactive protein (CRP) levels, fever, recurrent night sweats, anorexia. These patients were usually referred as inflammatory WM despite no definition has been established. Here, we describe clinical and biological characteristics of inflammatory WM patients, response to treatment, survival and discuss pathogenesis hypotheses. Methods In this descriptive retrospective study, we included WM patients followed at Saint-Louis hospital between 2007 and 2019 with WM diagnosis fulfilling the World Health Organization's criteria, with medullary infiltration proven by bone marrow biopsy or aspiration examination and monoclonal M paraprotein, associated with a biological inflammatory syndrome with or without clinical inflammatory signs. Inflammatory WM diagnosis was retained in the absence of differential diagnoses for the inflammatory syndrome such as cancer, infection, autoimmune or inflammatory diseases, using complete blood workup, PET and body scanner. Results Two-hundred and forty-two patients were included: 67 of inflammatory phenotype (28%), 166 non-inflammatory (68%) and 9 with inflammatory syndrome of unknown origin (4%). Describing inflammatory WM, diagnoses were made between 1985 and 2018, 50% after 2007. At treatment initiation, median age was 69 years (range 45-94), monoclonal IgM median value was 24.9 g/L (4.8-77.3) (Table 1). Median CRP was 40.5mg/L (IQR 23.8-64.8). CRP was correlated with fibrinogen (r =0.53, 95% confidence interval (CI) 0.18-0.76, p=0.006) and inversely correlated with albuminemia (r=-0.65, CI -0.82- -0.39, p < 0.001). Mean medullary infiltration was 50%. Three of 35 patients with avalaible karyotype had 6q deletion. Only 12 patients had medullary molecular analysis: 9 of them harboured MyD88 L265P mutation, 2 p53 mutations and none CXCR4 WHIM mutation. Five cryoglobulin tests were positive, Coombs test positive for 3 patients and anti-MAG antibodies positive for 2. Indications for front-line therapy were cytopenias in 44 patients (88%), inflammatory syndrome for 20 (40%), systemic symptoms in 15 (30%), tumoral syndrome in 10 (20%) and hyperviscosity syndrome in 3 (6%). Sixty-two patients were treated, at front-line 60% received rituximab-based therapy and 39% monotherapy. Overall response rate was 84%. Inflammatory and hematological response were statistically correlated (OR 13.8, CI 2.07-74.6, p = 0.005). Median follow-up was 12.6 years (IQR 7.0-22.8). Median progression-free survival (PFS) after front-line therapy was 32 months and estimated PFS was 68% (CI 55-78) at 10 months, 59% (CI 46-70) at 20 months and 30% (CI 19-42) at 5 years. Overall survival (OS) for inflammatory and non-inflammatory WM patients were not significantly different (median OS 14.0 and 16.4 years, respectively, c2 0,14, p=0,71, Figure 1). At 5 years, estimated OS was 85% (CI 71-93) inflammatory patients and 84% (CI 75-90) for non-inflammatory, at 10 years 66% (CI 48-79) and 70% (CI 58-79). Three patients were secondarily diagnosed with diffuse large B-cell lymphoma (DLBCL). Conclusions We reported 67 WM patients with inflammatory phenotypes, representing a third of WM patients in our cohort. Compared with literature, their clinical and biological characteristics do not differ from non-inflammatory WM patients, as well as response to treatment and PFS. There is no excess of transformation into DLBCL. Our inflammatory and non-inflammatory cohorts show no difference in terms of OS. Inflammatory response is strongly correlated with hematological response. Non-decrease of CRP level during treatment and increase of CRP during follow-up in inflammatory WM patients should be a warning sign for refractory disease or relapse. Further studies are needed to better delineate this sub-group of patients and explore its pathogenesis. Studying medullary cytokinic environment, WM cells, tumoral microenvironment and M paraprotein contributions could elucidate the underlying pathophysiological mechanisms involved. Disclosures Thieblemont: Roche, Hospita: Research Funding; Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Cellectis: Speakers Bureau.

scholarly journals Gestational trophoblastic neoplasia: A 6 year retrospective study

2014 ◽  
Vol 03 (01) ◽  
pp. 033-037 ◽  
Author(s):  
Sushruta Shrivastava ◽  
Amal Chandra Kataki ◽  
Debabrata Barmon ◽  
Pankaj Deka ◽  
Chidananda Bhuyan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Complete Remission ◽  
Risk Score ◽  
Single Agent ◽  
Response To Treatment ◽  
Gestational Trophoblastic Neoplasia ◽  
Response To Chemotherapy ◽  
Chemotherapy Patients ◽  
Line Chemotherapy

Abstract Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score </=6) received single agent chemotherapy with methotrexate or actinomycin D. Patients with high risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Front-Line Consolidation with Autologous Stem Cell Transplantation in Patients with Nodal Aggressive Peripheral T-Cell Lymphoma (PTCL). A Prospective Study of the GEL-TAMO.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2463-2463
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Reyes Arranz ◽  
Angel Leon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy ◽  
Gallium Scan

Abstract Background: Nodal aggressive PTCL have a poor prognosis with conventional chemotherapy regimens for aggressive non-Hodgkin lymphomas. Therefore innovative approaches are needed. Among them, strategies including consolidation with high-dose chemotherapy and autologous stem cell transplantation in front line therapy may improve the outcome of these diseases. Aim: To report the experience of a national cooperative group in 26 patients with aggressive nodal PTCL who underwent treatment including ASCT as consolidation of front line therapy. Patients and Methods: Twenty-six patients Gallium scan positive with nodal PTCL entered into the study: 11 cases of PTCL-unspecified (42%), 8 ALCL (31%) and 7 AIL (27%). Patients received three courses of MegaCHOP and subsequently were evaluated by CT scan and Gallium scan. Those patients Gallium scan negative received another course of MegaCHOP and then the transplant. Those patients Gallium scan positive after 3 courses of MegaCHOP received 2 courses of the IFE regimen (Ifosfamide 3.3g/m2 days 1–3 and Etoposide 300 mg/m2 days 1–3) and if at least achieved a partial response received the transplant otherwise they are out of the study. Median age was 44 years, 96% of the patients presented Ann Arbor stage III or IV; 54% presented B symptoms; 31% bone marrow involvement and 72% of the patients presented 2–3 factors of the a-IPI. Results: Thirteen patients (50%) achieved a CR after 3 courses of MegaCHOP and 12 patients received IFE as salvage therapy. Twenty patients out of the 26 initial patients were able to proceed to the transplant. After the transplant 85% of patients achieved a CR. The 6 patients who did not received the transplant was due to progression of the disease in 4 cases, lethal toxicity in one case and refusal in another case. With a median follow up of 35 months for alive patients, the overall survival (OS) and progression-free survival (PFS) at 3 years were 73% and 53%, respectively. OS, PFS and disease-free survival for the 20 patients who underwent the ASCT consolidation was 84%, 53% and 63%, respectively. Conclusion: Early salvage therapy for patients not in CR after 3 courses of chemotherapy and ASCT consolidation for chemosensitive patients may improve the outcome of patients with nodal aggressive PTCL. Larger series and longer follow up are needed to confirm this promising approach.

Long Term Follow-up of 121 Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Treated in Prospective GMALL Trials Supports a Greater Emphasis On Allogeneic SCT as Definitive Postremission Therapy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2608-2608 ◽  
Author(s):  
Heike Pfeifer ◽  
Christoph Wettner ◽  
Barbara Wassmann ◽  
Aristoteles A.N. Giagounidis ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
Elderly Patient ◽  
Elderly Patients ◽  
Research Funding ◽  
Intensive Chemotherapy ◽  
Front Line ◽  
Consolidation Chemotherapy ◽  
Line Therapy ◽  
Postremission Therapy

Abstract Abstract 2608 Background: Combined treatment with a tyrosine kinase inhibitor (TKI) and ALL-type induction and consolidation chemotherapy followed by allogeneic SCT is standard front-line therapy for younger patients with Ph+ALL, but the value of adding intensive chemotherapy to a TKI in elderly patients is controversial. More than 90% of elderly patients achieve a complete remission, irrespective of the type of TKI-based induction, but relapse is the major cause of treatment failure. In a previously reported randomized trial examining imatinib combined with intensive induction and consolidation chemotherapy for Ph+ALL in elderly patients (n=55), the probability of overall survival (OS) after 24 months was 42% ± 8% (Ottmann OG et al., Cancer. 2007; 109:2068-76). To date, very little published data on long-term outcome of elderly patients with Ph+ALL are available. Aims: We conducted the present analysis to determine whether subsets of patients derive long-term benefit from combined imatinib plus intensive chemoptherapy, examine the characteristics of long-term survivors, determine whether such patients can be identified by assessment of MRD, and obtain preliminary results on the feasibility and efficacy of SCT in this population of elderly patient. Study design and patients demographics: Our current analysis includes a total of 121 patients (119 ALL, 2 CML in lymphoid blast crisis), with a median age of 66 years (range 54–80). Fifty-five patients were enrolled in a previously reported randomized clinical trial comparing single-agent imatinib and chemotherapy as induction therapy, followed by up to 6 cycles of consolidation chemotherapy; a further 67 patients were subsequently treated according to this protocol as per recommendation by the GMALL Study Group. Results: The overall CR rate was 88%, median time to progression was 14.5 months (range 0.5–102) and OS was 18.6 months (range 0.5–102), respectively. Probabilities of remission duration, survival and TTP at 5 years were 19%, 22% and 19%, respectively. The type of initial induction therapy had no significant impact on OS and DFS. Of 113 pts, who were evaluable for comorbities, pulmonary disease was the only comorbidity associated with inferior outcome (median OS 13 months vs. 20 months, univariate analysis p=0.02). Allogeneic SCT was performed in CR1 in 12 patients and as salvage therapy in another 7 patients. Median age of these 19 patients was 62y (range 54–69). The time from diagnosis to SCT in CR1 was 4.6 months (2.9 mo – 16.8 mo) and from relapse to SCT in >CR1 3 months (2.1 mo – 6.1 mo). The 5yr OS in patients transplanted in CR1 vs. non-transplanted patients was superior (48% vs 22%). Remarkably, OS of the 7 patients transplanted beyond CR1 as part of salvage therapy was 43% after 4.5 years. With a median follow-up of 21.6 months (range 3.3– 54) after SCT, 8 patients are in ongoing CR with a median OS of 51.8 months from initial diagnosis (range 35 – 66), 5 pts. died in CR, 6 pts. relapsed. Conclusions: The combination of imatinib with intensive chemotherapy is feasible in elderly patients, but long-term survival is poor primarily due to high relapse rate. Allogeneic SCT in CR1 is superior to conventional therapy and should be considered as front-line therapy in this elderly patient population. The encouraging results of allogeneic SCT performed beyond CR1 suggest that SCT should be considered as definite postremission therapy in a larger proportion of elderly patients than is current practice. Disclosures: Ottmann: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

The Role of Angiopoietins System in Waldenstrom's Macroglobulinemia: Correlations with Marrow Microvessel Density and Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3901-3901
Author(s):  
Efstathios Kastritis ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Maria Gavriatopoulou ◽  
Dimitrios Christoulas ◽  
Athanasios Papatheodorou ◽  
...  
Keyword(s):  
Microvessel Density ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Waldenström’S Macroglobulinemia ◽  
Vessel Formation ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia ◽  
Angiogenic Cytokines

Abstract Abstract 3901 Angiogenesis is elevated in many hematological malignancies, but there is limited information for angiogenesis in Waldenstrom's macroglobulinemia (WM). Several cytokines including VEGF (and its major angiogenic component VEGF-A), bFGF, angiogenin and angiopoietin-1 (Ang-1) and 2 (Ang-2) participate in the neoangiogenesis process. We have previously shown that circulating angiogenic cytokines correlate with disease severity in WM (Anagnostopoulos et al, Br J Haematol 2007;137:560–8), while it has been reported that the bone marrow (BM) microvessel density (MVD) is increased in 30%-40% of patients with WM (Rajkumar et al, Semin Oncol 2003;30:265–9). The ratio of Ang-1/Ang-2 correlates with survival in multiple myeloma, but there is no information for the prognostic value of the angiopoietins and other angiogenic cytokines in WM. To address this issue, we studied the serum levels of VEGF, VEGF-A, bFGF, angiogenin, Ang-1 and Ang-2 in the serum of 55 patients with symptomatic WM before the administration of any kind of therapy, in 5 patients with asymptomatic WM (AWM), in 12 patients with IgM MGUS and in 30 healthy controls, of similar age and gender. Circulating VEGF, VEGF-A, bFGF, angiogenin, Ang-1 and Ang-2 were measured using ELISA method (R&D Systems, Minneapolis, MN, USA for VEGF, bFGF, angiogenin, Ang-1 and, Ang-2; Diaclone SAS, Besancon, France for VEGF-A). MVD was also evaluated in the BM biopsies of all patients, according to standard methodology. Table 1 depicts the levels of the studied angiogenic cytokines. The serum levels of VEGF, VEGFA, bFGF, angiogenin and Ang-2 were markedly elevated in WM patients compared to controls (p<0.001 for all comparisons); Ang-1 levels (p<0.01) were lower in WM patients than in controls, and the corresponding Ang-1 to Ang-2 ratio was significantly lower in WM patients than in controls, further indicating an angiogenic shift in WM patients. Circulating angiogenin (p<0.001) and Ang-2 (p=0.001) levels were also increased in WM patients compared to patients with IgM MGUS but Ang-1 levels were lower (p=0.003) resulting in Ang 1/2 ratio significantly higher in IgM MGUS than WM patients (p=0.004). In symptomatic WM patients, Ang-2 levels and the corresponding Ang-1/2 ratio correlated with serum beta2-microglobulin (r=0.454, p=0.002 and r=0.459, p=0.003, respectively). Ang-2 levels correlated with ISSWM stage (1914 ± 1175 pg/ml vs. 4461 ± 2628 pg/ml vs. 3926 ± 2172 pg/ml, for ISSWM-low, intermediate and high risk, respectively, p=0.007). A strong inverse correlation of MVD to Ang-1 was found in patients with WM (r=-0.600, p=0.011), indicative of the regulatory function of Ang-1 as an antagonist of vessel sprouting and new vessel formation. The median follow-up of symptomatic WM patients was 35 months. The median overall survival (OS) has not been reached yet, while the probability for 3-year OS was 76%. The median progression-free survival (PFS) was 57 months and the 3-year probability of PFS was 56%. Patients with Ang-2 levels above the median value had significantly shorter PFS (3-year PFS rate 82% vs. 50%, p=0.032; Figure). We conclude that in patients with WM, serum levels of several angiogenic cytokines (Ang-2, angiogenin, VEGF, VEGF-A, and bFGF) are markedly elevated and for some of these cytokines there is a correlation with disease features. The levels of pro-angiogenic cytokines, such as Ang-2 increase as disease evolves for IgM MGUS to symptomatic WM, while the Ang-1 decreases. We show that the MVD in the BM strongly correlates to decreasing Ang-1 levels, probably due to the decreasing inhibitory effect of Ang-1 to vessel formation in the BM microenvironment as disease evolves. For the first time we found that Ang-2, may also have a prognostic significance, associated with significantly shorter PFS. Further follow up is needed in order to evaluate the prognostic significance of Ang-2 for the OS of patients with WM Table: Levels of the studied circulating angiogenic cytokines (mean ± SD) Controls IgM MGUS aWM WM VEGF (pg/ml) 106 ± 76 323 ± 217 116 ± 83 399 ± 248 VEGF-A (pg/ml) 6.7 ± 13.6 97.5 ± 94 28.4 ± 49.3 113 ± 113 bFGF (pg/ml) 1.3 ± 3.2 12 ± 14 9.5 ± 16 17 ± 21.6 Angiogenin (pg/ml) 2.4×105 ± 0.5×105 2.7×105 ± 0.8×105 2.8×105 ± 0.7×105 4.5×105 ± 2.1×105 Ang-1 (pg/ml) 4.8×105 ± 1.1×105 4.8×105 ± 1.9×105 2.6×105 ± 1.5×105 2.5×105 ± 2.3×105 Ang-2 (pg/ml) 1747 ± 1023 1783 ± 684 3775 ± 1296 3424 ± 2570 Ang-1/2 ratio 28.1 ± 11.6 31 ± 14 6.5 ± 1.6 14.5 ± 17.7 Disclosures: No relevant conflicts of interest to declare.

Long-Term Outcome Of 151 Patients With Relapsed APL Receiving Second-Line With Chemotherapy Or Arsenic Trioxide-Based Regimens

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3922-3922
Author(s):  
Pau Montesinos ◽  
David Martínez-Cuadrón ◽  
Concha Rivas ◽  
Salut Brunet ◽  
José David González-San Miguel ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Salvage Therapy ◽  
Second Line ◽  
Front Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Chemotherapy Group ◽  
Line Therapy

Abstract Introduction Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The long-term outcome of salvage therapy using an ATO-based approach compared with chemotherapy based regimens is not well established. We analyze the clinical outcome of 151 APL patients relapsing after front-line therapy with ATRA and anthracycline, who received second-line therapy with chemotherapy or ATO-based regimens. Methods From June 1997 to May 2013, 151 patients (94 M/57 F; median age: 42 years, 2-81) relapsed after front-line therapy with PETHEMA trials. Patients presented with either molecular relapse (n=47) or hematological relapse (n=104). Sixty-seven patients (44%) followed salvage therapy with chemotherapy-based regimens (chemotherapy group) consisting of induction with mitoxantrone plus cytarabine plus ATRA (n=45), EMA (n=7), or other regimens (n=15). Patients not eligible for stem-cell transplantation (SCT) received consolidation with or without maintenance therapy. From October 2003, 84 patients (56%) received salvage therapy with ATO-based regimens (ATO group), comprising induction with ATO (0.15 mg/kg intravenously until CR, with ATRA [n=19] or chemotherapy [n=6]) followed by one consolidation cycle with ATO plus ATRA. If the post-consolidation bone marrow PCR was negative an autologous (auto)-SCT was recommended, when the PCR was still positive an allogeneic (allo)-SCT was planned. Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without low-dose chemotherapy. Results Baseline characteristics, including sex, relapse-risk at primary diagnosis, morphologic and BCR subtype, as well as age at relapse and type of relapse, were similar in both cohorts of patients. Although not significant, patients rescued in the chemotherapy group presented earlier relapses (<18 months after initial APL diagnosis) (55% vs. 43%, P=0.13). CR rates were 85% in the chemotherapy group (8 deaths and 2 resistances) and 92% in the ATO group (4 deaths and 3 resistances) (P=0.11). In patients achieving second CR, a molecular CR was achieved after consolidation in 78% and 84%, respectively (P=0.38). Twenty-two patients in the chemotherapy group (39%) and 16 in the ATO group (21%) were not transplanted in second CR (P=0.04). The reasons for not SCT in the chemotherapy and in the ATO group were ineligibility for SCT (6 vs. 8 patients), early relapse before planned SCT (10 vs. 7 patients), and mobilization failure (6 vs. 1 patients). Overall, 34 patients underwent SCT in the chemotherapy group (auto-SCT, 20; allo-SCT, 14), and 57 underwent SCT in the ATO group (auto-SCT, 47; allo-SCT, 10). The median follow-up in the chemotherapy group was 95 months (range, 24-167), and 33 months (range, 3-100) in the ATO group. The 5-year overall survival (OS), disease-free (DFS), and relapse-free survival (RFS) in the chemotherapy group and in the ATO group were 40% vs. 56% (P=0.01), 31% vs. 39% (P=0.07), and 34% vs. 48% (P=0.09), respectively. For patients not receiving SCT because of mobilization failure or ineligibility, the 5-year OS, DFS, and RFS in the chemotherapy group and in the ATO group were 56% vs. 19% (P=0.11), 42% vs. 19% (P=0.49), and 42% vs. 29% (P=0.63), respectively. For patients receiving auto-SCT, the 5-year OS, DFS, and RFS in the chemotherapy group and in the ATO group were 55% vs. 80% (P=0.04), 40% vs. 54% (P=0.06), and 44% vs. 57% (P=0.13), respectively. For patients receiving allo-SCT, the 5-year OS, DFS, and RFS in the chemotherapy group (P=0.48), and 31% vs. 57% (P=0.34), respectively. All but one patient underwent auto-SCT with negative PCR (this patient relapsed rapidly after auto-SCT). Regarding allo-SCT, 7 patients were PCR+ and 17 were PCR negative before SCT (5-year DFS 0% vs. 41%, respectively, P=0.01). Conclusions This study performed in a large series with prolonged follow-up of APL patients relapsing after upfront therapy with ATRA and anthracycline shows high rates of CR either with ATO (92%) or chemotherapy regimens (85%). Salvage therapy with ATO-based regimen allowed performing more frequently auto-SCT with negative PCR, and this strategy resulted in an overall improvement of the 5-year OS, DFS, and RFS. Disclosures: No relevant conflicts of interest to declare.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

Generation of a Large Observational Pan-European Data Platform for Treatment and Outcome Patterns in Patients with Waldenstrom's Macroglobulinemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2096-2096 ◽  
Author(s):  
Christian Buske ◽  
Shalal Sadullah ◽  
Efsthatios Kastritis ◽  
Giulia Benevolo ◽  
Ramon Garcia-Sanz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
United Kingdom ◽  
Czech Republic ◽  
Combination Therapy ◽  
Research Funding ◽  
Chart Review ◽  
Line Treatment ◽  
Front Line ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Introduction Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with a low incidence of ~3 cases per million per year. There are few randomized trials and no well-established treatment standards in WM. Treatment landscapes for treatment-naïve and relapsed WM are heterogeneous and data on treatment choices and their outcome in patients (pts) outside clinical trials are lacking. The goal of this project was to generate data on epidemiologic/treatment patterns and efficacy outcomes for WM over a prolonged period of time (~10 yr) in a large pan-European effort. Methods In this observational chart review, physicians completed a retrospective electronic record for pts who fit the following inclusion criteria: confirmed WM, symptomatic disease at treatment initiation, front line treatment initiated between Jan 2000-Jan 2014, and availability of complete clinical/biologic evaluation at diagnosis/initial therapy. Study endpoints included initial/subsequent lines of treatment, progression-free survival (PFS), and overall survival (OS). The number of pt records per country was prespecified to balance the distribution between European countries. Results Of 454 pt records reviewed, cases were from France (n=92), United Kingdom (UK; n=72), Germany (n=66), Spain (n=60), Italy (n=56), Greece (n=25), Netherlands (n=25), Poland (n=21), Austria (n=19), and Czech Republic (n=16). Data were summarized across 5 lines of treatment for 454, 397, 160, 61, and 26 pts, respectively. Median age at initiation of front-line treatment was 65 yr (range, 29-89); 61% were male. The most common reasons for initiating treatment at diagnosis were constitutional symptoms (58%), cytopenias (72%; anemia [69%]), and IgM-related symptoms (57%). Choice of therapy varied with line of treatment; monotherapy fell from 31% in front-line to 20%/21% in 2nd/3rd-line ( Table 1). Combination therapy with antibody increased from 40% in front-line to 64%/56% in 2nd/3rd-line. Across all lines, rituximab followed by cyclophosphamide, and to a lesser extent, chlorambucil, fludarabine, vincristine, and bendamustine, were the most common agents, excluding steroids, that were used as monotherapy or in any combination with use varying between countries (Table 1). Median PFS decreased with successive lines of treatment (29 vs 23 vs 16 mo), (Figure 1) and varied by country and choice of agents (Table 1). Median OS was 123 mo, but significantly lower in pts ≥75 yr (75 mo) or with high-risk IPSSWM risk score (91 mo) and similar for pts with low/intermediate risk groups. Considerable country-specific OS differences were noted. Other malignancies were reported in 12% after diagnosis of WM. Conclusions The retrospective chart review of WM pts treated in Europe shows that constitutional symptoms and anemia are the most common reasons for initiating therapy. Rituximab was the most commonly used agent across all lines of treatment. Outside clinical trials, monotherapy is widely used even at first relapse with notable differences between countries. This large observational dataset will be an important tool to improve understanding of treatment practice and survival of WM pts in Europe outside of clinical trials, as well as unmet medical needs in the community. Table 1. Use of Monotherapy or Combination Regimens and Median PFS in Front -, 2nd -, and 3rd-Line Settings Overall and by Country Country Number of Cases, n Monotherapy, % Combination Therapy With Antibody†, % Combination Therapy Without Antibody, % Median PFS,Months (95% CI) Front line 2nd line 3rd line Front line 2nd line 3rd line Front line 2nd line 3rd line Front line 2nd line 3rd line Front line 2nd line 3rd line Overall 454 397 160 31 20 21 40 63 56 28 14 21 29.0 (25-31) 23.0 (20-26) 16.0 (10-18) France 92 86 43 62 26 16 24 66 70 14 8 14 28.5 (22-32) 30.0 (20-37) 16.0 (9-32) United Kingdom 72 64 19 18 22 21 19 55 42 63 23 37 31.5 (25-36) 20.0 (11-35) 13.0 (9-33) Germany 66 52 18 9 8 22 61 81 50 30 8 11 36.5 (29-44) 24.0 (16-29) 8.0 (3-16) Spain 60 58 21 43 28 38 38 59 52 18 12 5 18.0 (15-25) 16.0 (12-24) 11.0 (9-24) Italy 56 47 20 20 17 15 57 68 70 23 6 15 30.5 (20-39) 30.0 (18-42) 17.0 (4-21) Eastern European* 37 30 12 8 13 8 32 40 0 60 47 92 33.0 (26-38) 20.0 (16-26) 20.5 (4-38) Smaller European** 71 60 27 35 22 26 56 67 63 7 12 11 23.0 (18-29) 16.0 (13-25) 16.0 (7-26) * Includes Czech Republic and Poland **Includes Austria, Greece, and Netherlands † Antibodies other than rituximab, <1% Figure 1. Figure 1. Kaplan-Meier PFS Estimates by Line of Treatment Disclosures Buske: CELLTRION, Inc.: Consultancy, Honoraria. Sadullah:Roche: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; NAPP: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; TEVA: Consultancy; Boehringer: Other: Travel, Accommodations, Expenses. Kastritis:Janssen: Consultancy, Other: Travel, Accommodations, Expenses. Garcia-Sanz:Janssen: Honoraria, Other: Travel, Accommodations, Expenses; Takeda: Honoraria, Other: Travel, Accommodations, Expenses; Novartis: Research Funding. Leleu:Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; LeoPharma: Honoraria; Chugai: Honoraria. Willenbacher:Celgene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Amgen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; CTI: Consultancy, Other: Travel, Accommodations, Expenses. Hajek:Amgen: Honoraria; Celgene: Consultancy; Janssen: Consultancy. Cheng:Pharmacyclics LLC, an AbbVie Company: Employment. Graef:Pharmacyclics LLC, an AbbVie Company: Employment, Membership on an entity's Board of Directors or advisory committees; AbbVie: Equity Ownership. Dimopoulos:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Genesis Pharma: Research Funding.

Treatment Patterns and Outcomes of DLBCL after Failure of Front-Line Immunochemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2683-2683 ◽  
Author(s):  
Umar Farooq ◽  
Matthew J Maurer ◽  
Stephen M Ansell ◽  
Tasha Lin ◽  
Grzegorz S. Nowakowski ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Patterns ◽  
Front Line ◽  
Factors Associated ◽  
Line Therapy ◽  
First Relapse

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is curable for the majority of patients treated with anthracycline based immunochemotherapy (IC). However, up to 40% of patients will relapse or require retreatment of DLBCL and outcomes are poor in this setting. Here we examine the incidence, treatment patterns and outcomes of relapsed DLBCL in the R-CHOP era. Methods: Patients were prospectively enrolled in the University of Iowa / Mayo Clinic SPORE Molecular Epidemiology Resource (MER) within 9 months of diagnosis and followed for relapse, retreatment, and death. Clinical management at diagnosis and subsequent therapies were per treating physician. This analysis includes patients with DLBCL or primary mediastinal B-cell lymphoma (PMBCL) who underwent front-line anthracycline based IC; patients with primary CNS lymphoma or PTLD were excluded. All relapse and re-treatments were verified by medical record review. Response to front-line therapy was retrospectively classified per 2007 Revised Response Criteria for Malignant Lymphoma from available clinical and radiology records. Unplanned consolidative radiation (RT) without biopsy proven disease after achieving PR from IC (N=21) was not classified as a relapse. Results: 1039 patients with newly diagnosed DLBCL or PMBCL and treated with IC were enrolled in the MER from 2002-2012. Median age at diagnosis was 62 years (range 18-92) and 577 patients (56%) were male. 647 patients (63%) had stage III/IV disease and IPI at diagnosis was 0-1 in 350 patients (34%), 2 in 305 patients (29%), 3 in 250 patients (24%) and 4-5 in 134 patients (13%). At a median follow-up of 59 months (range 1-148), 258 patients had relapse or retreatment of DLBCL of which 184 (71%) died. Incidence of relapse was 21.7% (95% CI: 19.3%-24.4%) at 2 years and 25.5% (95% CI: 22.9%-28.5%) at 5 years. In addition, the incidence of lymphoma related death without documented relapse or retreatment was 4.7% (95% CI: 3.6%-6.2%) at 2 years. At first relapse, 174 patients (67% of relapsed) received platinum based salvage therapy with 90 (52%) subsequently proceeding to autologous stem cell transplant (ASCT). 22 patients received CNS directed systemic therapy at relapse with 9 (41%) proceeding to transplant, and 43 received non-platinum-based salvage systemic therapy with 7 proceeding to transplant (17%), 15 patients received RT only as 2nd line therapy, and 4 were untreated. At a median follow-up of 56 months (range 6-121) post-transplant, 39 of 107 patients who underwent transplant remain in remission with a 2-year post-transplant progression-free survival of 45% (95% CI 37%-56%). Response to front-line IC was predictive of post-relapse outcome. Survival post-relapse was superior in the 162 patients with responsive disease (CR or PR) at the end of front-line IC (median OS 21.0 months) compared to the 88 patients who had stable or progressive disease (median OS 6.8 months, HR = 2.33, 95% CI: 1.73-3.14 p<0.0001). Transient response in midst of front-line IC was similar to no response. Patients achieving a CR or PR to front-line IC were more likely to proceed to ASCT at relapse (55%) compared to patients with either SD or PD at the end of front-line IC (25% and 17% respectively, p<0.0001). Other factors associated with poor survival at first relapse were relapse within 12 months of diagnosis (HR = 2.24, 95% CI: 1.57-3.18, p<0.0001), IPI at diagnosis of 3-5 (HR=1.51, 95% CI: 1.13-2.03, p=0.0058), and age > 60 (HR =1.51, 95% CI: 1.12-2.03, p=0.0064). There was no difference in survival at first relapse by cell of origin (HR = 1.13, 95% CI: 0.74-1.72, p=0.59). Conclusions: Most patients undergo therapy after relapsed/refractory DLBCL but only one-third receive ASCT. Outcomes following all treatments for relapsed/refractory DLBCL remain poor. Factors associated with adverse outcomes include refractory to front-line therapy, early relapse, baseline IPI and advanced age. These outcomes provide relevant historical control for the many novel agents being tested in this unmet need. Figure 1. Figure 1. Disclosures Farooq: Kite Pharma: Research Funding. Maurer:Kite Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Thompson:Kite Pharma: Research Funding.

scholarly journals Predictors of favorable response to implanted of ventriculoperitoneal shunt in patients with idiopathic normal pressure hydrocephalus

2020 ◽  
Vol 1 (1) ◽  
pp. 81-86
Author(s):  
Mario Emiliano Ricciardi ◽  
Ismael Calandri ◽  
Lucas Alessandro ◽  
Mauricio Farez ◽  
Juan Villalonga ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Retrospective Study ◽  
Normal Pressure Hydrocephalus ◽  
Ventriculoperitoneal Shunt ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Response To Treatment ◽  
Clinical Factors ◽  
A Prospective Study

Introduction: The indication of a ventriculoperitoneal shunt (VPS) is discussed in patients with idiopathic normal pressure hydrocephalus (iNPH), due to the heterogeneity of the response to treatment and the risks involved in neurosurgery. Objective: To search for clinical factors and complementary studies in order to determine predictors of a favorable response to the VPS placement in patients with iNPH. Methodology: A retrospective study of patients with probable iNPH (according to international guidelines) treated with VPS assisted in a neurological clinic from January 2014 to January 2017 was conducted. A univariate statisticalanalysis of the variables considered as possible prognostic factors was performed. Results: 58 patients were included. Women presented 3.68 times more chances of improvement after the VPS (p=0.019). Good response to the gait test was associated with better response to the VPS (p=0.024). Conclusions: Female sex and good response to the gait test could be considered as predictors of a favorable response to the VPS placement in patients with iNPH. A prospective study is necessary to achieve a homogeneous diagnostic evaluation and a more extensive longitudinal follow-up to evaluate the clinical evolution in this group of patients.

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