scholarly journals Immunotherapy by anti-GD2 antibodies in patients with primary high-risk neuroblastoma, primary resistant and relapsed disease: Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg experience

2021 ◽  
Vol 8 (3) ◽  
pp. 14-29
Author(s):  
I. V. Kazantsev ◽  
A. G. Gevorgyan ◽  
T. V. Yukhta ◽  
D. A. Drozdovskaya ◽  
P. S. Tolkunova ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Supportive Therapy ◽  
Response To Therapy ◽  
Late Relapse ◽  
Salvage Regimen ◽  
Pilot Studies ◽  
Line Therapy ◽  
Relapsed Disease

Introduction. The long-term event-free survival of patients with high-risk neuroblastoma (NB) receiving intensive complex therapy according to current russian standard do not exceed 40 %. Also, there is no standard tactics in patients with primary resistant and relapsed disease, most of them die due to disease progression. While, anti-GD2 immunotherapy (IT) proved to be effective in patients with high-risk NB, in Russian Federation this method is not generally available. There are currently two pilot studies ongoing in Raisa Gorbacheva Memorial Institute aimed to evaluate the effectiveness of anti-GD2 antibodies in high-risk NB patients.Aim of the study – describing a single-center experience of anti-GD2 IT in primary high-risk NB patients and patients with primary resistant and relapsed disease.Materials and methods. A total of 20 patients received anti-GD2 antibodies, 16 of them were included into pilot trials. The median age at IT initiation was 5 (3–17) years. In 13 cases the therapy was initiated in patients with high-risk disease after auto-HSCT, in 3 cases – in patients with 1st systemic relapse of primary resistant disease after 2nd-line therapy and haplo-HSCT, in 1 case – in patient with 2nd chemosensitive relapse after haplo-HSCT. Also, 3 patients with progressive chemoresistant disease received anti-GD2 antibodies as monotherapy (n = 1) or in combination with chemotherapy (n = 2) as salvage regimen.Results. Patients receiving anti-GD2 antibodies after auto-HSCT retain response to therapy in 11 of 13 cases with a median follow-up period of 15 (6–27) months, in 2 cases there was disease progression during or immediately after IT cessation. Both patients with disease progression responded well to salvage therapy. Two of 3 haplo-HSCT recipients with prior good response to 2nd-line therapy are currently in remission 16 and 36 months past haplo-HSCT, one patient progressed 55 months after transplantation. A patient with 2nd late relapse after haplo-HSCT currently maintains remission on IT. Both patients with chemorefractory progressive disease did not respond to IT and died due to disease progression. IT was characterized by acceptable toxicity. In most cases it was complicated by Gr 1–2 fever, rash or neuropathic pain effectively controlled by supportive therapy. However, three patients had signs of neurotoxicity requiring therapy termination in one case.Conclusion. Dinutuximab beta IT is characterized by acceptable toxicity. With a median follow-up of 18 (6–59) months the majority (14 of 17) patients receiving anti-GD2 antibodies as maintenance therapy after auto- or allogeneic HSCT retain response. However, we did not observe any response in patients with progressive chemorefractory disease.

scholarly journals New risk model is able to identify patients with a low risk of progression in systemic sclerosis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001524
Author(s):  
Nina Marijn van Leeuwen ◽  
Marc Maurits ◽  
Sophie Liem ◽  
Jacopo Ciaffi ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
High Risk ◽  
Disease Progression ◽  
Risk Model ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Expert Assessment ◽  
Risk Of Progression

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine and Melphalan (FM) Reduced Intensity Conditioning (RIC) for High-Risk AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 838-838
Author(s):  
B. Oran ◽  
R. Saliba ◽  
S. Giralt ◽  
D. Couriel ◽  
A. Carrasco-Yalan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
High Risk ◽  
Disease Progression ◽  
Disease Status ◽  
Independent Effect ◽  
Donor Type

Abstract RIC with FM has extended the use of HSCT to patients otherwise not eligible for this treatment. Longer follow-up and larger number of patients now allow for more robust evaluation of risk factors and outcomes. Herein are the results of such an evaluation. Patients and Methods: We evaluated outcomes of 112 patients with high-risk AML/MDS treated from August 1996 to December 2003 with FM (fludarabine 100–180 mg/m2 and melphalan 100–180 mg/m2) and unmanipulated HSCT. Eligibility included age &gt;54 yrs. or comorbidity precluding an ablative preparative regimen. Disease status at HSCT was relapsed/refractory (n=43, 38.4%), primary induction failure (n=32, 28.6%), untreated (n=7, 6.3%) or complete remission (CR, n=30, 26.8). Cytogenetic risk was intermediate (n=59, 53%), high (n=47, 42%), low (n=3, 2.5%) or unknown (n=3, 2.5%). Donors were HLA matched related (MRD; n=59) or unrelated (UD; n=53). GVHD prophylaxis was tacrolimus based in all but one patient. Anti-thymocyte-globulin was added in 31 UD HSCT. Stem cell sources were bone marrow (n=56) or peripheral blood (n=57). Median age was 55 (range 22–74). Evaluated were the following variables and their influence on disease progression and overall survival: - age, donor type, duration of first CR, disease status at transplant (categorized as CR, No CR with (NoCR/CB) and without circulating blasts (NoCR/NoCB)), cytogenetics, acute and chronic GVHD (time dependent variables), and blood counts on day 30 (lymphocytes, monocytes and platelets). We used a Cox’s regression analysis. Results: Median time of follow up among survivors (n=43) was 28.4 mo (3.3–88.9). CR rate at day 30 post transplant was 87% (n=97), 8 patients died early and 7 did not respond. 25 (26%) of 97 patients progressed after day 30. All but 3 patients relapsed within the first year post HSCT, and only one relapsed more than 2 years after HSCT. In a landmark analysis, disease status at transplant was the only significant risk factor for progression among these 97 patients (HR of 3.7 for the NoCR/CB group compared to the CR group). 69 of 112 patients died with a median survival of 4.6 mo. Seven deaths (10% of all deaths) were observed more than 2 yrs. after HSCT, due to GVHD (n=3), infection (n=2), relapse (n=1) and unknown causes (n=1). Two-year OS and PFS was 44% and 69% respectively. Disease status at HSCT and grade II-IV aGVHD were the only significant predictors of OS on univariate and multivariate analysis. Blood counts on day 30 were associated with disease status at transplant, donor type and aGVHD. Their independent effect on outcome could not be evaluated given sample size. Conclusion: A significant portion of older patients with high-risk AML/MDS may achieve long-term PFS, but early relapses are the major cause of treatment failure in this context. Prognostic factors for event-free and overall survival Variables Multivariate analysis for disease progression CB=circulating blasts Disease status n Events (n) HR 95% CI p 2-yr PFS CR 30 6 1.0 57% (39–72) NoCR/NoCB 41 7 1.1 0.4–3.2 0.9 46% (30–60) NoCR/CB 26 12 3.7 1.4–9.8 0.001 22% (9–38) Multivariate analysis for overall survival (OS) Disease status HR 95% CI p 2-yr OS CR 30 12 1.0 66% (48–80) NoCR/NoCB 49 29 1.8 0.9–3.5 0.06 40% (26–53) NoCR/CB 34 28 2.8 1.4–3.5 0.002 23% (11–37) gd II-IV aGVHD 2.8 1.8–4.6 &lt;0.001

Excellent Immune Recovery Following the Intensive Chemotherapy CODOX-M/IVAC, An Effective Therapy for HIV-Associated Burkitt’s Lymphoma (BL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3612-3612
Author(s):  
Silvia Montoto ◽  
Jamie Wilson ◽  
Kate Shaw ◽  
Maureen Heath ◽  
Andy Wilson ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Stage Iii ◽  
Concomitant Treatment ◽  
Immune Recovery ◽  
Intensive Chemotherapy ◽  
End Of Treatment ◽  
High Risk Disease ◽  
Immunological Recovery

Abstract Background and aim: The outcome of patients with HIV-associated Burkitt’s lymphoma (HIV-BL) treated with infusional regimens remains poor, even in the highly active anti-retroviral (HAART) era. In contrast, promising results have been published in HIV-BL with the same intensive chemotherapies used in the non-HIV population. However, scarce data on immunological recovery following these regimens are available. The objective of this multicentre study was to analyse the outcome of patients with HIVBL treated with the intensive chemotherapy regimen CODOX-M/IVAC and HAART, with a particular emphasis on the analysis of immunological recovery after treatment. Patients and methods: 29 patients (22 male; median age: 38) from 3 UK centres consecutively treated with CODOX-M/IVAC from 2003 to 2008 were included in the study. CODOX-M/IVAC consisted of 2 alternating cycles of CODOX-M (cyclophosphamide 800mg/sqm day 1 and 200mg/sqm days 2–5, doxorubicin 40mg/sqm day 1, vincristine 1.5mg/sqm days 1 and 8, methotrexate 3g/sqm day 10) and IVAC (etoposide 60mg/sqm days 1–5, ifosfamide 1g/sqm days 1–5, cytarabine 1g/sqm bd days 1 and 2) for patients with high-risk disease and 3 cycles of CODOX-M for patients with low-risk disease. High-risk disease was defined by the presence of at least 2 of the following: stage III–IV, ECOG≥2, extranodal sites≥2 or high serum LDH. All patients received concomitant treatment with HAART (NRTI + NNRTI: 21; NRTI + PI: 8) and prophylactic antimicrobials as well as intrathecal prophylaxis and G-CSF as per protocol. Four patients received rituximab in combination with the chemotherapy. Lymphocyte subsets and plasma HIV-1 viral load (VL) were measured during chemotherapy and at 3-month intervals during follow-up. Results: HIV was diagnosed concomitantly with BL in 12 patients. The median CD4 count at BL diagnosis was 167/mm3 (range: 4–848), with CD4>200/mm3 in 41% of patients and VL being undetectable in 5 (18%) patients. Eight (28%) of the patients previously known to have HIV infection were on HAART before the diagnosis of BL. The majority of the patients (72%) had high-risk disease. Twenty patients (69%) were diagnosed in advanced stage (III–IV), with bone marrow (BM) involvement in 6 (21%) and central nervous system (CNS) infiltration in 5 (17%). The International Prognostic Index (IPI) was high (3–5) in 14 (48%) patients. Grade 3–4 non haematological toxicity was as follows: infection, 66% of the cycles; mucositis, 12%; and diarrhoea, 13%. Nine patients died during treatment, due to disease progression in 3 cases, toxicity in 5 (3 infections, 2 GI bleeding) and 1 patient died with a CNS lesion that was not biopsed. Response at the end of treatment amongst 23 assessable patients was as follows: complete response (CR)/CR uncertain (CRu): 16 patients (69%); partial response (PR): 4 (17%); progression: 3 patients (13%). After a median follow-up of 17 months (range: 9–67), 17 of 20 responding patients remain alive without disease progression, whilst 2 patients (1 CR, 1 PR) relapsed at 2 and 1 months after finishing treatment and died. One HAART non-compliant patient died in CR of HIV-related causes. Three patients in PR at the end of treatment survive without evidence of disease progression at 28, 37 and 51 months. Overall survival (OS) and disease-free survival (DFS) at 3 years were 49% and 70% respectively. Blood samples for immune recovery analyses were available for the majority of the patients during follow-up (81% 6 months after finishing chemotherapy, 86% at 12 and 24 months). VL was undetectable in 85% and CD4>200/mm3 in 53% of assessable patients 6 months after completing chemotherapy. Time (no. patients at risk) % CD4>200/mm 3 VL undetectable no./no. assessed % no./no. assessed % At BL diagnosis (29) 12/29 41 5/28 18 1 month after finishing chemotherapy (21) 5/17 29 10/15 67 6 months after finishing chemotherapy (16) 8/15 53 11/13 85 12 months after finishing chemotherapy (14) 9/12 75 10/12 83 Conclusions: This retrospective analysis demonstrates that the intensive regimen CODOX-M/IVAC is feasible and effective in HIV positive patients on HAART with BL. Immunological recovery after treatment, not previously reported after such intensive chemotherapy, is excellent. Whether concomitant treatment with rituximab will improve outcome warrants further study.

Final Analysis of a Randomized Comparison of ABVD Chemotherapy with a Strategy That Includes Radiation Therapy (RT) in Patients with Limited-Stage Hodgkin Lymphoma (HL): NCIC CTG/ECOG HD.6

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 590-590 ◽  
Author(s):  
Ralph M. Meyer ◽  
Mary Gospodarowicz ◽  
Joseph M. Connors ◽  
Robert G Pearcey ◽  
Woodrow A Wells ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Board Of Directors ◽  
Final Analysis ◽  
Primary Analysis ◽  
Advisory Committees ◽  
Limited Stage ◽  
Risk Patients ◽  
Single Modality

Abstract Abstract 590FN2 Background: The NCIC CTG / ECOG HD.6 trial is based on the hypothesis that for patients with limited-stage HL, treatment with single-modality ABVD provides comparable disease control, is associated with a reduced incidence of deaths due to late treatment effects and thus might improve long-term survival in comparison with treatment that includes extended-field RT. In this randomized controlled phase III trial, our primary objective was to compare the 12-yr overall survivals (OS) of limited-stage HL patients treated with ABVD alone with those receiving therapy that includes RT. Secondary outcomes include freedom from disease progression (FFDP), in which those dying prior to disease progression are censored, and event-free survival (EFS), in which the first of disease progression or death is considered an event. In 2005, we published 5-yr outcomes (median follow-up 4.2 yrs [Meyer, J Clin Oncol]). We now report results of the final analysis. Methods: Eligible patients had non-bulky clinical stage I-IIA HL; patients with subdiaphragmatic disease were eligible if disease was confined to the iliac, inguinal and/or femoral regions. Prior to randomization, patients were stratified into low and high-risk categories; low-risk patients had all of lymphocyte predominant or nodular sclerosis histology, age < 40 yrs, ESR < 50, and involvement of 3 or fewer disease-site regions; all others were high-risk. Patients randomized to therapy that includes RT received single-modality subtotal nodal irradiation (STNI) if low-risk and combined-modality ABVD (2 cycles) plus STNI if high-risk. All patients randomized to the experimental arm received single-modality ABVD (4 cycles); those not demonstrating a complete remission with restaging after 2 cycles received 6 cycles. Between March 1994 and April 2002, 405 patients were entered; 399 were eligible and included in the primary analysis (modified intent–to-treat [ITT]). The clinical cut-off date for follow-up was 2010/DEC/31 and the database was locked on 2011/JUL/15. All P-values are 2-sided. Results: The median duration of follow-up is 11.3 yrs. The OS was superior in patients randomized to ABVD (P=.04; HR=0.5; 12-yr estimates 94% vs. 87%). In comparison with patients randomized to therapy that includes RT, FFDP trended to being inferior in patients randomized to ABVD (P=.07; HR=1.82; 12-yr estimates 88% vs. 92%); no differences in EFS were detected (P=.5; HR=0.87; 12-yr estimates 86% vs. 80%). Sensitivity analyses included a true ITT evaluating all randomized patients and adding data obtained between the clinical cut-off and data-lock dates; results were robust and yielded similar findings. Causes of death in ABVD vs. RT-arm patients (N = 12 vs. 24) included HL or early treatment complication (6 vs. 4), second cancers (4 vs. 9), and other (2 vs. 11). Analysis of high-risk patients allocated to ABVD (N=137) vs. ABVD+STNI (N=139) showed similar respective results to the primary analysis: in comparison with those randomized to RT, OS was superior in the ABVD arm (12-yr estimates 92% vs. 81%; HR=.47; P=.04), FFDP was inferior (12-yr estimates 87% vs. 94%; HR=3.03; P=.01) and no differences in EFS were detected (12-yr estimates 84% vs. 78%; HR=.87; P=.6). Late-effects trended to being less frequent in ABVD patients, including second cancers (6.1% vs. 10.8%) and cardiac events (9.7% vs. 14.8%). Conclusions: We conclude that in patients with limited-stage HL, ABVD improves OS as compared with treatment that includes STNI, including combined modality therapy, because it is associated with fewer deaths from causes other than HL. The HD.6 trial hypothesis was thus confirmed. With respect to modern RT approaches, the implications of our results are: i) at 12 years, 88% of patients are disease-free and more than 90% are alive when initially treated with ABVD alone; ii) limitations exist in using FFDP as a proxy measure for OS when late treatment effects may occur; and, iii) when treatment strategies have competing risks, long-term follow-up provides crucial insights into the interpretations of best therapy. Disclosures: Connors: Seattle Genetics: Consultancy, Research Funding. Horning:Genentech: Employment, Equity Ownership. Crump:Millennium Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ortho Johnson & Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

A Long-Term Follow-up Report on Autologous Hematopoetic Cell Transplant (AuHCT) for Patients with Hodgkin Lymphoma — Limited Utility of Post-Transplant Surveillance Computerized Axial Tomography (CAT scan) and/or PET Scan,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4205-4205
Author(s):  
Henry C. Fung ◽  
Sunita Nathan ◽  
Neel B. Shah ◽  
John J. Maciejewski ◽  
Elizabeth Shima Rich ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Pet Scan ◽  
Late Relapse ◽  
Cell Transplant ◽  
Post Transplant ◽  
Cat Scan ◽  
Long Term Follow Up

Abstract Abstract 4205 Background: Autologous Hematopoetic Cell Transplant (AuHCT) is the treatment of choice for patients with relapsed or refractory Hodgkin Lymphoma. Approximately 40–60% of patients achieve a durable response and possible cure after the transplant with progressive disease accounts for most of the treatment failures. CAT scan +/− PET scan are usually performed before AuHCT and repeated post-transplant to assess responses. As part of the long term follow-up; post-transplant surveillance CAT scan +/− PET scan are often performed with intent to detect early disease progression and possible early intervention. Here, we attempt to evaluate the utility of this approach by examining the patterns of treatment failures for patients with Hodgkin Lymphoma who received AuHCT. Patients/Methods: A retrospective chart review was performed. Between 01/94 and 12/06, 55 consecutive patients with refractory or relapsed Hodgkin Lymphoma underwent autologous HCT at our institution. All patients underwent a CAT scan and FDG-PET before AuHCT and approximately 2–3 months following the transplant to evaluate the response to HCT. As part of the long-term follow-up; post-transplant surveillance CAT scan were performed every 3–6 months for 2–3 years, then every 6–12 months up to 5 years post-transplant. Results: A total of 55 patients were followed post autologous HCT. The median age at HCT was 32 (ranging from 15–66); 27 were male. Seventeen patients had primary progressive HL and 38 had relapsed HL. Eighteen patients had extra-nodal disease at disease progression. With a minimal follow-up of 4 years (range 4 to 7 years) for living patients; 40 patients are alive and well with no evidence of disease. Thirteen patients developed disease progression after transplant at a median of 3 months (range 0 – 32 months) post-HCT. All the disease progression developed within the first 7 months after transplant except 2 who developed late relapse 28 and 32 months post-HCT. Fifteen patients died with 10 from progressive disease and 5 from non-relapse causes: auto accident: 1, breast cancer (incident diagnosed of late recurrent Hodgkin lymphoma): 1, AML:1 and 2 from chronic graft versus host disease after salvage allogeneic HCT. All 55 patients underwent PET scan evaluation 2–3 months after HCT to evaluate post-HCT responses. Twenty-nine patients had no evidence of PET activity post transplant, while 26 patients had evidence of activity. While there were 2 subsequent progressions in the PET negative group (1 of them was a late relapse), there were 9 progressions in the PET positive group. The 5-years estimated survival was 65%. Conclusion: In summary: 1) Most of the disease progressions after AuHCT for relapsed and refractory Hodgkin Lymphoma occurred within the first seven months after the transplant and were associated with abnormal first post-transplant CT +/− PET scan. Thus, the utility of long term surveillance radiological studies is very limited and is not recommended. 2) With longer follow-up, long-term complications including second cancer replace disease as the primary cause of treatment failure. This underscores the importance of long-term follow-up for HCT long-term survivors. Disclosures: No relevant conflicts of interest to declare.

Essential Thrombocythaemia in Young Adults: Clinical Characteristics and Outcomes – a Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5060-5060
Author(s):  
Grace Kam ◽  
Richard Yiu ◽  
Ai Leen Ang ◽  
Yvonne SM Loh ◽  
Yeh Ching Linn ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Disease Progression ◽  
Young Patients ◽  
Medical Attention ◽  
Thrombotic Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Thrombosis Rate

Abstract Abstract 5060 Less than 20% of patients with essential thrombocythemia (ET) are diagnosed below the age of 60. Patients with ET have increased risk of thrombosis and bleeding and potential for progression to myelofibrosis (MF) or acute myeloid leukaemia (AML). In limited studies of young patients, the clinical course has been relatively benign with low rates of transformation to AML or MF. Thrombohemorrhagic events are generally few, but higher than that of the general population. This study aims to characterize of a group ET patients diagnosed at age ≤40, their thrombotic and hemorrhagic events, disease progression and treatment given. Patients were identified through a single institution MPN registry. This is an IRB approved registry that captures comprehensive information about patients with ET. Data on patient demographics, treatment, and disease-related events were obtained. Patients were diagnosed from 1975–2011, using either WHO or PVSG criteria depending on date of diagnosis. Kaplan-Meier method was used for survival analysis. 59 patients were diagnosed with ET at age ≤40. Median age of diagnosis was 31. 5years (range 16–40), with a median follow up of 7. 7years (0. 4–33. 8). All were of Asian descent: 81. 4% Chinese, 11. 9% Malay, 3. 4% Indian and 3. 4% Filipino. 40. 7% were male. JAK2 V617F mutation was screened for in 61%. Of these patients, 11 were positive, 25 negative for the mutation. Mean presenting counts were: WBC 10. 7 × 109/L (5. 9–21. 3), Hb 13. 6g/dL (9. 7–16. 4), platelets 957 × 109/L (449–2377). Splenomegaly was noted in 3 patients. 20. 3% had underlying hypertension, 16. 9% hyperlipidemia and 5. 1% diabetes mellitus. One patient had a prior stroke. Another had prior portal vein thrombosis. At diagnosis, 23. 7% were symptomatic, with microvascular symptoms of headache (11. 9%) and giddiness (6. 8%) being most common. The remainder were diagnosed incidentally, on health screening or when seeking medical attention for unrelated conditions. One patient presented with a myocardial infarction at diagnosis, while another had a significant bleeding post hemorrhoidectomy with drop in Hb by >2g/dL (platelet 2457 × 109/L). Based on a history of prior thrombosis, 3 patients were defined as high risk for thrombotic events. 67. 8% of patients had cytoreduction, indications being platelets ≥1500 × 109/L (n=16), presence of risk factors for atherosclerotic disease (n=11) and history/onset of thrombosis (n=5). In 8, the reason for cytoreduction could not be ascertained. Hydroxyurea was most commonly used (62. 7%), followed by anagrelide in 52. 5% and interferon 25. 4%. 5. 1% received busulphan, and 1. 7% 32P. Use of antiplatelet therapy was noted in 83. 8%, most frequently aspirin (76. 5%) and ticlopidine (11. 9%). On follow up, 2 arterial thromboses occurred (stroke, TIA), giving a thrombosis rate of 0. 39%/patients/year. Neither was a recurrent thrombosis. No venous thrombosis or major bleeds occurred. 20. 4% had minor mucocutaneous bleeding; 5 had platelets ≥1500 × 109/L at that time. 3. 4% had disease progression due to MF and another 3. 4% had AML. 3. 4% of patients died due to AML. Median survival was 33. 8years (95% confidence interval 30. 3–35. 5). Initial blood counts, presence of JAK2 and high risk disease status did not correlate with thrombotic risk, risk of death or disease progression. Use of antiplatelet agents and a platelet count ≥1500 × 109/L did not correlate with bleeding risk. Few studies have looked exclusively at young patients with ET. In this group, most patients were asymptomatic and well, ET being diagnosed incidentally. They were predominantly at low risk for thrombosis and other ET-related complications. The period of follow up was comparable to that of other studies and during that time, the rate of complications and risk of disease progression was low. The thrombosis rate of 0. 39% per patient year was less than that reported by other groups (2. 2–2. 6 thromboses/100patients/year) (Leukaemia 2007;21:1218–1223, Clin Appl Thrombosis/Hemostasis 2000;6(1):31–35) but similar to the 0. 74%/patient year reported by Barbui (Blood. Epub. June 13 2012). Overall findings generally complemented those reported by other groups. No risk factors were found to influence the occurrence of complications, but the number of events was small. Follow up of this group of patients over time is essential to see if their disease course remains benign or if complications will increase with time. Soli Deo Gloria Disclosures: Kam: Shire Pharmaceuticals: Consultancy, grant to support the MPN registry Other.

Treatment Patterns & Survival In Multiple Myeloma Patients Sequentially Exposed To Thalidomide, Bortezomib & Lenalidomide In a UK Single Centre

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5380-5380 ◽  
Author(s):  
Julie L Tarant ◽  
John Ashcroft ◽  
Sylvia Feyler ◽  
Roger G Owen ◽  
Christopher Parrish ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Response To Therapy ◽  
High Dose ◽  
Second Line ◽  
Single Centre ◽  
Line Therapy ◽  
Wide Range ◽  
Duration Of Response

Abstract Background In recent years, the introduction of the immunomodulatory drugs (IMiDs) thalidomide & lenalidomide & the proteasome inhibitor (PI) bortezomib has substantially improved the therapeutic options & prolonged survival of patients (pts) with multiple myeloma (MM). Current treatment strategies involve sequential exposure to these agents, though the most effective sequencing of exposure has yet to be determined. MM is still, for the majority of pts, a relapsing & incurable disease with poor survival outcomes & alternative treatment approaches in relapsing disease after exposure to currently available novel agents is an on-going unmet need. We report the results of extended follow-up in this patient cohort. Objectives We examined outcomes in pts with progressive disease following sequential exposure to thalidomide, bortezomib & then lenalidomide, to assess responses to these & subsequent therapies in a “real-life” single centre setting. Methods Pts were eligible for this retrospective study if they had received sequentially thalidomide-, bortezomib- then lenalidomide-based combination therapy (LenCom) for MM as per The National Institute for Health & Care Excellence (NICE) guidance. Case records were examined for diagnostic details, depth & duration of response to PI treatment & regimens employed. T0 was defined as the time point at which LenCom was discontinued, whether for progressive disease (PD) or intolerance (I). Response to therapy subsequent to T0& Progression Free Survival/Overall Survival (PFS/OS) were assessed & factors predicting outcome analysed (e.g. ISS stage at diagnosis, age, previous therapies received, previous depth & length of response to treatment). Results Between Jan’07-Sept’12, 55 pts (27 Male & 28 Female) were enrolled. Median age at diagnosis was 59 yrs (range 33-89);ISS scores were: 20% stage I, 28% stage II & 28% stage III (23% unclassified). The median number of lines of therapy prior to LenCom was 3 (range 2-6). First line therapy was thalidomide-based in 64%; 36% underwent ASCT & 4 pts underwent tandem ASCT/RIC AlloSCT. Second line therapy was bortezomib-based in 42% &  53% pts received lenalidomide as > 4th line. Median time from diagnosis to commencing LenCom was 52.5mns (range 4-146). 43 pts (77%) had reached T0 (PD n=29, I n=14). At a median of 66 mns follow up (range 12-162 mns), a median of 9 cycles (range 1-32) of LenCom were administered to all pts & 7 cycles (range 1 -32) to those who had discontinued LenCom. Dexamethasone was discontinued after median 12 cycles in pts reaching T0, being stopped in 28% (median 6 cycles before T0). Median PFS from commencement of LenCom was 16.2 mns. At 4 mns median follow-up post T0, a total of 26 pts have received therapy after T0, of whom 3 received lenalidomide-based treatment (11.5%) & 3 received bortezomib-based treatments (11.5%). Thalidomide based treatment was received by 13 pts (combined with Bendamustine in 3 & bortezomib in 2). Post-T0 pts also received clinical trial therapies (3 pts on SRT501 trial, 1 pt on pomalidamide companion study & 1 pt on KW2478 – a heat shock protein 90 inhibitor), thalidomide-based treatment (10 pts, 2 with bortezomib), & high dose dexamethasone. 13 pts (50%) demonstrated PD as maximum response to first post-T0 therapy. Duration of response was generally very limited (median 0 mns, range 0-6 mns). Second line post T0 treatments, including pomalidomide, were received by 12 pts with only 2 pts pts achieving a PR or better to Thalidomide & bortezomib based regimens. Third line post T0 treatments were given to 2 pts with 1 pt achieving a further brief PR to DT-PACE. With a median follow-up of 6.4mns (1-37), 31 pts have died (PD n=18, infection n=6, other n=7). Median OS from diagnosis & commencement of LenCom were 100 mns & 18.4 mns, respectively. Median OS from T0 was 3.9mns (range 0-33 mns), influenced by the b2-microglobulin at T0 (<vs.³ 3.0 mg/L: 9 vs. 4.8 mns, p=0.027). The depth of response to LenCom correlated with PFS (P<0.001) but not post-T0OS (p=0.68). Conclusion Pts with MM who have relapsed after sequential exposure to thalidomide, bortezomib & lenalidomide have very limited treatment options. At present, a wide range of treatments are used, including re-challenging with lenalidomide, bortezomib & trial based treatments. However, few pts achieve a meaningful response to therapy & survival is consequently extremely poor. Disclosures: No relevant conflicts of interest to declare.

Late Relapse in Hodgkin Lymphoma (HL): A Retrospective Analysis of Patients Enrolled on Clinical Trials at the Istituto Nazionale Tumori of Milan (INT-MI)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2697-2697 ◽  
Author(s):  
Simonetta Viviani ◽  
Alberto Mussetti ◽  
Oreste Di Bartolo ◽  
Antonello Cabras ◽  
Pinuccia Valagussa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Retrospective Analysis ◽  
Salvage Therapy ◽  
Prognostic Score ◽  
Late Relapse ◽  
First Line ◽  
First Line Therapy ◽  
Conventional Dose ◽  
Line Therapy

Abstract Background The majority of relapses in HL occur within the first three years from end of first-line treatment. Late relapses, occurring after more than five years, are rare events and there is no consensus on the optimal treatment. Aims of study The aim of our retrospective analysis was to assess the proportion of relapses occuring > 5 years in patients enrolled on clinical trials at INT-MI between 1974 and 2007, to evaluate prognostic factors, treatment outcome and survival. Patients and Methods From 1974 to 2007, 1089 consecutive HL patients, previously untreated with chemotherapy (CT), were enrolled on clinical trials at the INT-MI; 959 patients in complete remission (CR) after first-line CT or combined modality treatment were included in this study. In all patients who relapsed >5 years from end of frontline treatment a second biopsy was performed to prove HL histology at relapse. Failure-free survival (FFS) was calculated from the date of late relapse until documented relapse from CR after salvage therapy, disease progression during or within 3 months from end of salvage therapy, or death, whichever came first. Overall survival (OS) was calculated from the date of late relapse to last follow-up visit or death. Results A total of 31 complete responders after first-line therapy relapsed after > 5 years. Median time from end of first-line therapy to relapse was 115 months (range, 63-299). Main patient characteristics at late relapse were as follows: males: 71%; median age: 48 years (range, 20-67); classical histology: 81%; stage III/IV: 55%; B Symptoms: 48%; extranodal disease: 26%; > 3 involved sites: 52%; bulky disease: 13%; GHSG prognostic score ³ 1: 52%; MSKCC prognostic score ³ 1: 61%. Conventional dose salvage chemotherapy (CT) was delivered to 64.5% of patients: 9 patients were retreated with the same regimen employed as front-line therapy (MOPP alternated with ABVD), 5 were retreated with ABVD alone, 6 received non cross-resistant regimens. High-dose chemotherapy (HDCT) with hematopoietic stem cell reinfusion (ASCT) was delivered to 35.5% of patients. With a median follow-up of 9 years, 10-year FFS was 57% (95% Confidence Interval CI: 33-75) and OS was 64% (95% CI: 41-80). In univariate analysis only age > 48 years was associated with an inferior FFS [44 % (95% CI:18-68) vs 92% (95% CI:54-99), p=<0.001] and OS [40% (95%CI:16-65) vs 100% , p=0.03]. There was no significant difference in the outcome of patients treated with HDCT+ASCT compared to those treated with conventional dose CT [FFS 75% (95%CI: 30-93) vs 63% (95%CI: 36-82), p=0.78; OS 71% (95%CI: 26-92) vs 64% (95%CI: 34-83),p=0.21]. Conclusions: This retrospective cohort of patients with late relapse HL is to date one of the largest case series and with the longest follow up. Besides the rarity of these cases, late relapse of HL appears to have a good prognosis. Classical prognostic scores for relapsed HL have no role in this setting. In the subgroup analyses, being older than 48 years conveys a worse prognosis. HDCT and ASCT does not appear to confer an important survival advantage over conventional dose CT. Figure 1. Figure 1. Disclosures Viviani: Takeda Italia SpA: Consultancy; Teva Italia SpA: Consultancy; Italfarmaco SpA: Consultancy; Takeda International: Consultancy. Corradini:Celgene: Consultancy; Novartis: Consultancy.

Long-term follow-up of BMT CTN 0702 (STaMINA) of postautologous hematopoietic cell transplantation (autoHCT) strategies in the upfront treatment of multiple myeloma (MM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8506-8506 ◽  
Author(s):  
Parameswaran Hari ◽  
Marcelo C. Pasquini ◽  
Edward Allen Stadtmauer ◽  
Raphael Fraser ◽  
Mingwei Fei ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Phase Iii ◽  
Second Primary ◽  
Long Term Outcomes

8506 Background: STaMINA was a phase III trial comparing progression-free survival (PFS) among 758 pts randomized to: 1. second autoHCT then lenalidomide (Len) maintenance (Auto/Auto, n = 247); 2. consolidation with Len/bortezomib/ dexamethasone (RVD) followed by Len maintenance (Auto/RVD, 254); 3. Len maintenance (Auto/Len, 257). All three arms were similar (Stadtmauer JCO 2018). Len maintenance was designed to continue for 3 years and amended to allow continuation until disease progression through a follow up protocol (07LT, NCT#02322320). We report 6 yr follow up for STaMINA and the results of Len discontinuation beyond 3 years. Methods: 07LT was offered to pts who were progression-free at 38 mo; completed planned Len maintenance and were within 4 years of BMT CTN 0702 follow up. Among 431 07LT eligible patients, 273 enrolled and 179 opted to continue maintenance until disease progression. All patients enrolled in STaMINA were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and long-term outcomes for patients not enrolled on 07LT (N = 166) were available through this mechanism. Before combining 07LT data and CIBMTR data for LTFU analysis, outcomes in both databases were analyzed separately and confirmed to be comparable. Results: Using intent-to-treat (ITT), 6yr PFS and overall survival (OS) was the same among Auto/Auto (43.9%; 73.1%), Auto/RVD (39.7%, 74.9%) and Auto/Len (40.9%, 76.4%)(p = 0.6; p = 0.8). Protocol defined high risk disease, (HR = 1.53, p < 0.0001) and age (p = 0.03) were adverse risks for PFS. In as treated analysis, 6yr PFS were 49.4%, 39.7% and 38.6% for Auto/auto (170), Auto/RVD (222) and Auto/Len (361), respectively (p = 0.01). 6yr PFS in high risk pts as treated analysis were 43.6% and 26% for Auto/auto and Auto/Len, respectively (p = 0.03). Landmark analysis at 38 mo included 215 pts who continued Len maintenance (either on 07LT study or commercial Len) vs. 207 who stopped. Baseline demographics; study arm on 0702, induction pre-autoHCT were similar. Len discontinuation after 38 mo was associated with inferior PFS (79.5% vs. 61% at 5yr; HR = 1.91, p = 0.0004) but similar OS. Incidence of all second primary malignancies (SPM)(81 cases with 43 heme-malignancies) was associated with age. Conclusions: Long term outcomes are similar using ITT, but as treated analysis suggested a PFS benefit for tandem autoHCT, driven mainly by pts with high risk MM. Len discontinuation even at 38 mo was associated with inferior PFS. Clinical trial information: NCT02322320 .

scholarly journals MON-LB83 The Initial Dose of 131I as a Potential Independent Predictor for Residual/Relapsed Disease in Pediatric Differentiated Thyroid Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Carmen L Bustamante Escobar ◽  
Yong Bao
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Initial Dose ◽  
Risk Group ◽  
Risk Category ◽  
Intermediate Risk ◽  
The Mean ◽  
Relapsed Disease ◽  
Disease Free

Abstract Introduction: In the guidelines for management of pediatric Differentiated Thyroid Cancer (DTC) 131I therapy is recommended for treatment of iodine-avid persistent locoregional disease that cannot be resected as well as iodine-avid distant metastases. To date, no consensus has been reached regarding the 131I dose for treatment of DTC in children. We report our institutional experience and highlight the initial dose of 131I as a potential independent predictor of residual/relapsed disease. Methods: We performed a retrospective analysis of all pediatric patients diagnosed with DTC between 2010 and 2018. The cohort included all patients up to 21 years of age, with minimal length of follow-up of 24 months. The risk stratification was done following the American Thyroid Association guidelines for pediatric DTC. We defined residual/relapsed disease as detectable thyroglobulin and positive anatomical lesions in imaging studies during the follow-up period. The log-rank test was used to evaluate disease-free survival. The P value was set at &lt; 0.05. Results: Among 59 eligible patients, females were 69.5% (n=41) and males were 30.5% (n=18). The mean age at diagnosis was 16 years (9-21 years). All patients were alive at follow-up (median, 42 months; range 24 to 144 months). Fifty-eight patients had classic papillary thyroid cancer (PTC) and only 1 patient had follicular thyroid cancer. Among the patient with PTC, 39.6% (23/58) had follicular-variant PTC, 8.6% (5/52) had diffuse-sclerosing PTC and 17.2% (10/58) had other variants. Nineteen (32%), 30 (51%), and 10 (17%) had low-risk, intermediate-risk, and high-risk disease, respectively. Within the Low-risk group, 68% (13/19) received 131I. The mean initial dose was 60.9 mCi [26-150 mCi]. Eighty four percent (11/13) received ≤100 mCi and 27% (3/11) had residual/relapsed disease. Fifteen percent (2/13) received &gt;100 mCi and none had residual/relapsed disease. Sixteen percent (1/6) of patients without 131I therapy had residual/relapsed disease. (P=0.48) Within the Intermediate-risk group, all 30 patients received 131I. The mean initial dose was 97.5 mCi [27.3-215 mCi]. Sixty percent (18/30) received ≤100 mCi and 38.8% (7/18) had residual/relapsed disease. Forty percent (12/30) received &gt;100 mCi and 16.6 % (2/12) had residual/relapsed disease. (P=0.15) Within the High-risk group all 10 patients received 131I. The mean initial dose was 159.9 mCi [129.3-384 mCi]. Fifty percent (5/10) received ≤150 mCi and 60% (3/5) had residual/relapsed disease. Fifty percent (5/5) received &gt;150 mCi and 20% (1/5) had residual/relapsed disease. (P=0.2) Conclusion: There are no statistical differences of disease-free rate between the initial dose of 131I among all risk categories. However, the use of more than 100 mCi in the intermediate-risk category and more than 150 mCi in the high-risk category may be recommended.

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