Prophylactic Rh and Kell Antigen Matching Significantly Decreases Rates of Alloimmunization in Transfusion Dependent MDS Patients

Abstract Background: 40-80 % of patients with myelodysplastic syndrome (MDS) become transfusion dependent during their disease course and are at risk for the development of alloimmunization. Red blood cell (RBC) alloantibodies can make finding compatible blood for transfusion more difficult, expensive and time consuming. Allommunization rates of approximately 30-47% have been reported in patients with sickle cell disease and the transfusion of RBCs prophylactically matched for Rh antigens E and C, and K antigens reduced the rate of alloimmunization from 3% to 0.5% per unit (Vichinsky et al, 2001). In 2007, our hospital instituted a policy of transfusing prophylactic Rh and K matched blood to MDS patients. The objectives of this study were to compare the rates of alloimmunization in MDS patients who received prophylactic Rh and K matched blood compared to those that did not and identify potential risk factors for alloimmunization. Methods: 193 Transfusion dependent MDS patients were identified out of 387 patients registered and prospectively followed in a local MDS registry. Transfusion dependence was defined as the receipt of at least 1 unit of PRBC every 8 weeks for a minimum of 16 weeks. Records of transfusions received up to May 1, 2014 were collected from blood bank databases of the hospitals at which patients were transfused. Patients were classified according to whether phenotyping had been performed, the location of transfusions (transfused only at our institution, transfused only at an outside institution or transfused at both sites) and whether prophylactic Rh (E, C antigens) and K matched blood was transfused. Data were descriptively analyzed and we conducted univariate and multivariate logistic regression using p< 0.05 as statistically significant to identify risk factors for alloimmunization. Results: 176 MDS patients with complete transfusion records are included, 73 transfused at Sunnybrook, 92 transfused in community hospitals and 11 at both. The median age was 72 yrs (range 22-89), 60% were male, and 8%, 43% and 27% had very low, low and intermediate risk R-IPSS scores respectively. Median follow up was 2.9 years (IQR 1.6-5) 3.49 SD). Blood groups O, A, B, AB and O were 45%, 38%, 15% and 2% respectively, while 85% were RhD+. The median time from diagnosis until first transfusion was 4 months (IQR: 0.2-14), with 51 patients having received at least 1 transfusion prior to diagnosis at a median time of 0.9 months. 4.5% had a pre-existing allo-antibody at time of MDS diagnosis. With a median follow up from diagnosis of 3 years (IQR:1.6-5)), the median number of RBC units transfused was 38 (IQR: 15-98)) and 36 (20%) patients developed new alloantibodies (median 2 (IQR (1-2.5) alloantibodies). The median number of RBC units until first allo antibody was 13.5 units (range 0-121) and 1.25 years from diagnosis (95% CI:0.4-2.1). The majority of the alloantibodies were in the Rh (n=28) and K (n=14) groups (80%) and co-existed 27% of the time. More patients transfused at our hospital received prophylactic Rh K matched blood sometimes or always (60% versus 26%) and rates of allo-immunization were decreased by 65% (absolute rate of alloimmunization 10% versus 29%). By multivariate analysis analysis, number of rbc transfused (p<.0001), receiving prophylactic phenotype matched blood (p=.0008) and location of transfusions (Sunnybrook versus elsewhere (p=.03)) were independent risk factors for alloimmunization. Conclusions: 20-30% of RBC transfusion dependent MDS patients will become allo-immunized to clinically significant blood group antigens, the majority being Rh and K antigens. The practice of phenotyping at baseline and prophylactically transfusing Rh and Kell matched blood decreases rates of alloimmunization up to 65% and should be strongly considered for routine transfusion practice in centres that treat MDS. Table 1. All Patients (n=176) Sunnybrook (n=73) Community(n=92) Ever phenotyped 45% 64% 28% Phenotyped before 1st transfusion 20% 38% 8% Developed allo-antibodies 20% 10% 29% Received prophylactic Rh K matched blood (developed alloantibodies) Never Sometimes Always 58% (16%) 24% (42%) 18% (6%) 40% (3%) 23% (23%) 37% (7%) 74% (22%) 22% (60%) 4% (0%) Figure 1. Allo Antibody free survival according to number of red cell units transfused in patients that developed an allo-antibody Figure 1. Allo Antibody free survival according to number of red cell units transfused in patients that developed an allo-antibody Disclosures Wells: Celgene: Honoraria, Other, Research Funding; Novartis: Honoraria, Research Funding; Alexion: Honoraria, Research Funding. Buckstein:Celgene: Research Funding.

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Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Blood ◽

10.1182/blood-2021-154492 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3935-3935

Author(s):

Shanee Chung ◽

Jennifer White ◽

Cynthia L. Toze ◽

Heather J. Sutherland ◽

David Sanford ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Median Number ◽

Salvage Chemotherapy ◽

Brentuximab Vedotin ◽

Relapse Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

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Observational Prospective Registry for the Assessment of the Clinical Impact of Starting Anti-Myeloma Treatment at Biological Relapse

Blood ◽

10.1182/blood.v124.21.4765.4765 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4765-4765

Author(s):

Adrian Alegre ◽

Merche Gironella ◽

Juan Miguel Bergua ◽

Esther Gonzalez ◽

Fernando Escalante ◽

...

Keyword(s):

Bone Marrow ◽

Board Of Directors ◽

Median Time ◽

Research Funding ◽

Marrow Transplant ◽

Clinical Relapse ◽

First Line ◽

Advisory Committees ◽

Free Survival

Abstract Introduction: Despite the great medical advances associated with the introduction of thalidomide, bortezomib (BORT), and lenalidomide (LEN) for the treatment of multiple myeloma (MM), it remains an incurable disease. Most patients (pts) show disease progression, consistent with the clinical evolution of MM, and only a low percentage achieve long-term responses and extended progression-free survival (PFS). The heterogeneous nature of MM in both the clinical and biological setting is reflected in the heterogeneity of MM relapses. The International Myeloma Workshop Consensus Panel (Rajkumar, Blood 2011) states that treatment (Tx) shall begin either at clinical relapse with symptoms (clinR), or in the event of asymptomatic relapse with significant paraprotein relapse, biological relapse (BR). The purpose of this Spanish registry is to describe MM relapse patterns comparing the impact of Tx decisions in pts who meet the criteria for biological relapse (BR) according to IMWG criteria with those in whom Tx was delayed until clinical relapse (clinR). Here, the preliminary results of this study are presented. Methods: MM pts in (or previous to) first or second BR who have achieved ≥ PR since their last Tx are eligible for inclusion in this observational prospective registry at the time BR is detected. Evaluations performed at least bi-monthly are mandatory. A total of 41 Spanish sites participated in the registry following approval from their independent ethics committees, with 410 pts expected to be included, without physician’s decision of prescribing Tx affecting the inclusion. The main objective of the registry is to assess the time to progression (TTP) from the start of anti-MM Tx at the onset of asymptomatic BR vs. the start of Tx at the time of clinR. Secondary objectives are to describe demographics of BR; to assess the median time elapsing from BR to clinR; to assess overall response rate (ORR), event-free survival (EFS), PFS, overall survival (OS) at BR and at clinR (if appropriate); to asses safety and quality of life (QoL) using 2 validated questionnaires (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-MY24); to document the tolerability profile of the Tx; and to describe the use of associated resources. Here, we summarize baseline characteristics and preliminary results from 83 pts (out of 126 registered pts) who had basal data in the registry at the time of this report. Results: Overall, 79% of pts presented with a BR and 21% were in a bi-monthly watchful waiting follow up. The mean age of pts was 67 years, 53% were female, 57% were in first relapse, 43% and 27% had an ECOG performance status (PS) of 0 and 1, respectively, while the ECOG PS was unknown in 30% of pts at the time of this report. In total, 30% of pts had ISS stage I, 26% had ISS stage II, and 22% had ISS stage III, while ISS stage data were not available or unknown for 12% and 10% of pts, respectively. MM types were IgG Κ (37% of pts), IgG λ (23%), IgA Κ (13%), IgA λ (9%), and type was unknown in 17% of pts. 28% of IgG/IgA MM types were Bence-Jones. Cytogenetic risk assessments were available in 66% of pts. Among those pts with a BR, 51% received active Tx without waiting for a ClinR. First-line Tx was BORT-based in 70% of pts. Overall, 55% of pts had undergone autologous stem cell transplantation, 15% had received consolidation Tx and 34% had received maintenance Tx. After first-line Tx, 17% of pts achieved a stringent complete response (sCR), 31% achieved a CR, 24% achieved a very good partial response (VGPR), and 10% achieved a PR. The median time to BR was 24.53 months. Most (63%) pts who registered after second relapse received LEN-based Tx. Conclusions: To our knowledge, this is the first prospective study in MM to evaluate BR as well as the effects of Tx based on the decision to start Tx at BR vs. clinR. In this preliminary cohort, the physicians’ decision to start active Tx at BR, before the onset of clinR in 50% of cases, was noteworthy. Further follow-up is needed to identify the differences between these two strategies. Updated clinical results will be presented at the meeting. MM-BR Study, Spanish Myeloma Group-GEM/PETHEMA Bibliography Alegre A, et al. Haematologica. 2002;87:609-14. Brioli A, et al. Blood. 2014;123:3414-9. Fernández de Larrea C, et al. Bone Marrow Transplant. 2014;49:223-7. Lenhoff S, et al. Haematologica. 2006;91:1228-33. Rajkumar SV, et al. Blood. 2011;117:4691-5. Zamarin D, et al. Bone Marrow Transplant. 2013;48:419-24. Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lahuerta:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ruiz:Celgene: Celgene Stock options as part of the employee's compensation plan Other, Employment. Vilanova:Celgene: Contracted by Celgene Other.

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TRANSFUSION PRACTICE, POST-TRANSFUSION COMPLICATIONS AND RISK FACTORS IN SICKLE CELL DISEASE IN SENEGAL, WEST AFRICA.

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2022.004 ◽

2022 ◽

Vol 14 (1) ◽

pp. e2022004

Author(s):

Moussa Seck ◽

Alioune Badara Senghor ◽

Mossane Loum ◽

Sokhna Aissatou Touré ◽

Blaise Félix Faye ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Median Number ◽

Transfusion Practice ◽

Red Cell ◽

Cell Disease ◽

Hiv Antibodies ◽

Transfusion Complications

Context and Objectives: Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. We aim to assess infectious markers, red cell alloimmunization and iron overload secondary to BT in SCD patients. Materials and Methods: This is a case-control study included 253 SCD (153 SCD-transfused and 100 SCD non-transfused). We evaluated the transfusion practice (modalities, indications), post-transfusion complications (infections, alloimmunization, iron overload) and risk factors of these complications (socio-demographic, clinical, biological). Results: Median age was 28.5 years (5 - 59). Sex ratio was 0.86. Homozygous SCD was more common (95.3%). Simple BT was performed in 92.8% and transfusion exchange in 18.9%. Transfusion indications were dominated by acute anemia (57.06%) and vaso-occlusive crisis (VOCs) (14%). Red blood cell concentrates (RBC) were administered to 93.46%. Median number of RBC received per patient was 10 (2 - 48). The prevalence of VHC in SCD-transfused was 1.33% and 2% for VHB. Anti-HIV antibodies were not found. Red cell alloimmunization frequency was 16%. The most common alloantibodies were anti-rhesus (34.19%) and anti-Kell (23.67%). Iron overload was detected in 7.84%. The number of RBC transfused was the only risk factor for alloimmunization (p = 0.03) and iron overload (p = 0.023). BT frequency was not related to infectious transmission. Conclusion: Despite advances in blood safety, BT therapy is still a risk for SCD polytransfused patients. Although infectious transmission has rare, the risk of alloimmunization and iron overload is high in these patients.

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Ibrutinib Dose Reduction Does Not Affect Progression-Free Survival in Patients with Waldenstrom Macroglobulinemia

Blood ◽

10.1182/blood-2018-99-111626 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1598-1598

Author(s):

Jorge J. Castillo ◽

Joshua Gustine ◽

Andrew Keezer ◽

Kirsten Meid ◽

Toni Dubeau ◽

...

Keyword(s):

Dose Reduction ◽

Median Time ◽

Research Funding ◽

Regression Models ◽

Progression Free Survival ◽

Free Survival ◽

Waldenstrom Macroglobulinemia ◽

Major Response ◽

Dose Reductions

Abstract Introduction: Ibrutinib is an oral Bruton Tyrosine Kinase inhibitor, approved for the treatment of symptomatic Waldenstrom Macroglobulinemia (WM). MYD88 and CXCR4 mutations affect progression-free survival (PFS) in patients with WM. In some cases, ibrutinib dose reductions are needed for the management of toxicity. However, it remains unclear if ibrutinib dose reductions adversely affect PFS in WM patients. Methods: We evaluated 217 consecutive patients with the clinicopathological diagnosis of WM who were symptomatic and received treatment with ibrutinib. We analyzed relevant clinical features and their association with the risk of dose reduction, using logistic regression models, as well as PFS using Cox proportional-hazard regression models. Time to events was estimated using the Kaplan-Meier method. p<0.05 were considered statistically significant. Results: All 217 patients were initiated on ibrutinib monotherapy at the approved dose of 420 mg by mouth (PO) once daily (QD). At a median follow-up of 26 months (95% CI 22-31 months), 159 patients (73%) continued ibrutinib without dose-reduction, while 58 (27%) patients had a decrease in their ibrutinib dose. There was no difference in follow-up between those with and without dose reduction. Of the 58 patients that dose reduced, 45 (78%) were reduced to 280 mg daily; 12 patients (21%) were reduced to 140 mg daily, and 1 (2%) to 140 mg every other day. The median time to ibrutinib dose reduction from 420 mg PO QD to 280 mg PO QD was 155 days (95% CI 89-282 days), and median time to dose reduction from 280 mg PO QD to 140 mg PO QD was 55 days (95% CI 24-260 days). Reasons for ibrutinib dose reduction included cytopenia(s) (n=13; 24%), arrhythmia (n=9; 17%), musculoskeletal discomfort (n=8; 15%), constitutional symptoms (n=6; 11%), skin changes/rash (n=5; 9%), mouth sores (n=4; 7%), gastrointestinal symptoms (n=3; 6%), infections (n=3; 6%), bleeding (n=2; 4%) and transaminase elevation (n=1; 2%). Patients in whom ibrutinib dose reduction was needed were more likely to be older than 65 years (76% vs. 47%; p<0.001), had higher International Prognostic Scoring System for WM (IPSSWM) at ibrutinib initiation (IPSSWM 1, 2 and 3 were 19%, 23% and 58% vs. 24%, 39% and 37%, respectively; p=0.03), and were more likely to have attained a major response (93% v. 69%; p<0.001) than patients in whom ibrutinib dose was not reduced. There were no differences in baseline characteristics including sex, hemoglobin levels, platelet counts, beta-2-microglobulin levels, serum IgM levels, bone marrow involvement, previous treatment, MYD88 and CXCR4 mutational status and time from WM diagnosis to ibrutinib initiation between those with and without dose reduction. Regression analyses showed higher odds of dose reduction occurring in patients >65 years (OR 3.6, 95% CI 1.8-7.1; p<0.001) and those who had attained a major response (OR 6.0, 95% CI 2.1-17.5; p=0.001). The median PFS for the entire group was not reached, and the 3-year PFS rate was 76% (95% CI 68-83%). Factors associated with a worse PFS were platelet count <100 K/uL (HR 3.9, 95% CI 1.8-8.7; p=0.001) and CXCR4 mutations (HR 3.0, 95% CI 1.5-6.0; p=0.001). Expression of mutated MYD88 (HR 0.01, 95% CI 0.00-0.09; p<0.001) and attainment of major response (HR 0.23, 95% CI 0.12-0.43; p<0.001) were associated with a better PFS. Importantly, those who experienced a reduction in their ibrutinib dose showed no significant difference in PFS (HR 1.19, 95% CI 0.61-2.35; p=0.61; Figure 1A). There were no differences between patients who reduced to 280 mg PO QD (HR 1.0, 95% CI 0.5-2.2; p=0.99) or 140 mg PO QD (HR 1.9, 95% CI 0.7-5.5; p=0.22) versus those without dose reduction (Figure 1B). Conclusion: Ibrutinib dose reduction occurred in 27% of patients with WM, at a median time to dose reduction of 155 days. Patients older than 65 years and those with major responses were more likely to have a dose reduction. With a median follow-up time of 26 months, ibrutinib dose reduction did not significantly impact PFS. Figure 1. Figure 1. Disclosures Castillo: Millennium: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Genentech: Consultancy. Hunter:Pharmacyclics: Consultancy. Treon:Johnson & Johnson: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Research Funding; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding.

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Frontline Hyper-CVAD with Ponatinib for Patients (pts) with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Results of a Phase II Study

Blood ◽

10.1182/blood.v126.23.2496.2496 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2496-2496

Author(s):

Koji Sasaki ◽

Susan O'Brien ◽

Farhad Ravandi ◽

Deborah A Thomas ◽

Haim G Moore ◽

...

Keyword(s):

Overall Survival ◽

Median Time ◽

Research Funding ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Event Free Survival ◽

Vascular Events ◽

Free Survival ◽

Philadelphia Chromosome Positive

Abstract Background: Addition of tyrosine kinase inhibitors (TKIs) to chemotherapy improves outcome in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib is a more potent BCR-ABL inhibitor, and covers the T315I clones. The combination of hyper-CVAD with ponatinib may contribute to better response rates and higher likelihood of eradication of minimal residual disease (MRD) than those reported with other TKIs. Methods: Pts with newly diagnosed Ph+ ALL received 8 cycles of hyper-CVAD alternating with high dose methotrexate and cytarabine every 21 days. Ponatinib was given at 45 mg/day for the first 14 days of cycle 1 then continuously for the subsequent 7 cycles. Pts in CR received maintenance with ponatinib 45 mg/day and vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely. Results: From 11/2011 to 9/2013, 34 pts with untreated Ph+ ALL and 3 pts previously treated (2 pts not in CR were treated with one cycle of chemotherapy before the detection of BCR-ABL1; 1 pt in CCyR after 2 cycles of chemotherapy and dasatinib) have received a median of 6 cycles (2-8); 13 are receiving maintenance in CR; 9 underwent ASCT after a median of 4 cycles. Baseline pt characteristic and outcome are described in table 1. The overall CCyR, MMR, and CMR rates were 100%, 95%, and 78%, respectively. The median time to MMR and CMR were 3 (range, 2-14) and 11 (range, 2-96) weeks, respectively. The median time to MRD negativity was 3 weeks (range, 3-14). Median time to platelet and neutrophil recovery for cycle 1 was 22 and 18 days, respectively, and 22 and 16 days for subsequent cycles. Grade ≥ 3 toxicity included infections during induction (54%), increased liver functional tests (38%), thrombotic events (8%), myocardial infarction (14%), hypertension (16%), skin rash (22%), and pancreatitis (22%). With a median follow up of 26 months, 29 (78%) remain alive and in CR. Six pts died in CR: 1 pt died in CR from an unrelated cardiac event after being taken off therapy and placed on imatinib, 1 from MOF (C2D13), 1 from NSTEMI (C2D41; ponatinib 45 mg daily), 1 from potential MI (C4D42; ponatinib 30 mg daily), 1 from head injury sustained after a fall (C4D13), and 1 from sepsis post ASCT. Two (5%) in CMR relapsed with no identifiable T315I mutations after a median of 18 months. One of these pts achieved a second CR after blinatumomab and dasatinib therapy. To date, 13 pts are receiving maintenance therapy in CR. After the increased incidence of vascular toxicities was recognized, we offered our pts the option to switch TKIs or to reduce the dose of ponatinib to 30 mg and further decreased to 15 mg in pts in CMR. Thirteen pts remained on ponatinib at a dose of 15 mg daily in 12 and 30 mg daily in 1 (transcript levels of 0.04%). No further vascular events were observed in pts receiving lower doses of ponatinib. Nine pts elected to switch TKIs to dasatinib (n=7), nilotinib, or imatinib (1 each). One pt was lost to follow-up. Of 9 patients who underwent ASCT while in first CR (7 with MMR and 2 with CMR before transplantation), all but one are alive and disease-free after transplantation. There was no difference in OS by whether patients were censored or not at the time of ASCT. After transplantation, TKI therapy was resumed in all but one patient (1 imatinib, 4 dasatinib, 1 nilotinib, and 1 ponatinib). The 2-year event-free and overall survival rates are 81% and 80%, respectively (Figures 1). Conclusion: The combination of hyperCVAD with ponatinib is highly effective in pts with Ph+ ALL. Due to the vascular events observed, the ponatinib dose was modified to 30 mg daily during consolidation with subsequent reduction to 15 mg in pts in CMR without further episode of cardiovascular events. Table 1. Patient characteristic and outcome N(%); Median [range] N= 37 Age (yr) 51 [27-75] Age ≥50 20 (54%) Age ≥60 12 (32%) Performance status, No. (%) 0-1 31 (84) 2 6 (16) WBC (x 109/L) 8 [1-630] Presence of CNS disease, No. (%) 3 (8) CD20 positivity, No. (%) 11 (30) Type of BCR-ABL1 transcript, No. (%) p190 27 (73) p210 10 (27) Cytogenetics abnormality, No. (%) Diploid 5 (14) Philadelphia-chromosome positive 32 (86) Baseline cardiovascular risk factors, No. (%) Hypertension 18 (49) Dyslipidemia 4 (11) Coronary artery disease 4 (11) Peripheral arterial disease 1 (3) Overall response, No. (%) CR 36/36 (100) CCyR 32/32 (100) MMR 35/37 (95) CMR 29/37 (78) Flow negativity 35/36 (97) Early death 0 Figure 1. a) Event-free survival, b) overall survival Figure 1. a) Event-free survival, b) overall survival Disclosures O'Brien: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Chahoud:American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Wierda:Glaxo-Smith-Kline Inc.: Research Funding; Celgene Corp.: Consultancy.

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Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis

Blood ◽

10.1182/blood-2021-151808 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2465-2465

Author(s):

Christopher J. Forlenza ◽

Jaclyn Rosenzweig ◽

Audrey Mauguen ◽

Ilia Buhtoiarov ◽

Branko Cuglievan ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Salvage Therapy ◽

Research Funding ◽

Pediatric Patients ◽

Median Number ◽

Brentuximab Vedotin ◽

Refractory Disease ◽

Free Survival ◽

Frontline Therapy

Abstract Background: Although the prognosis for children with Hodgkin lymphoma (HL) is excellent, up to 25% of patients experience relapse and require salvage therapy. Event-free survival (EFS) for patients with relapsed or refractory disease (R/R) who require high-dose therapy with autologous stem cell transplantation (ASCT) is between 31-67% (Daw, 2011), and efforts to improve these outcomes are an area of urgent clinical need. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate combined with monomethyl auristatin E. The phase III AETHERA study (NCT01100502) was a randomized, placebo-controlled trial that demonstrated consolidation with BV following ASCT for adults with R/R HL improved progression-free survival (PFS) in comparison to placebo (5-year PFS 59% vs. 41%) in patients identified as having a high-risk of post-ASCT progression (Moskowitz, 2015, 2018). However, there is limited data on post-ASCT BV consolidation in pediatric patients. Here, we report a retrospective multi-center study of BV as consolidation post-ASCT in pediatric patients with R/R HL. Patients and Methods: We performed a retrospective analysis of pediatric patients aged ≤ 21 years who received BV as consolidative therapy following ASCT for the treatment of relapsed/refractory HL. Data was collected on disease risk factors (refractory disease or relapse ≤ 12 months after frontline therapy, best response of partial remission or stable disease to salvage therapy, presence of extranodal involvement, presence of B symptoms, and number of systemic treatments pre-ASCT ≥ 2), treatment history, BV-related toxicity, and response to therapy. The primary endpoint was 3-year EFS. Events were defined as relapse, progression of disease, or death from any cause. Results: Seventy patients were identified from 14 academic centers. Eighteen received BV >90 days after ASCT and were excluded due to significant delay in initiation of BV. Of the remaining 52 patients, the median age at diagnosis was 15 years (range 4-21), and the median age at diagnosis of R/R disease was 16 years (range 8-22). Twenty-eight patients (54%) were male, 13 (25%) had B symptoms, 19 (37%) had extranodal disease. Six patients (12%) had primary refractory disease and 24 patients (47%) relapsed <12 months after frontline therapy. The median number of salvage regimens received pre-ASCT was 2 (range 1-7). Forty-two patients (81%) received BV as part of a pre-ASCT salvage regimen, 4 (8%) of whom did not receive BV in the regimen immediately prior to ASCT. Radiation therapy was used pre or post-ASCT in 16 patients (31%). Prior to ASCT, 40 patients (77%) were PET-negative (Deauville 1-3), 11 (21%) were PET-positive (Deauville 4-5), and response in 1 (2%) was unknown. The median time from ASCT to the start of BV consolidation was 52 days (range 30-90 days). The most frequent adverse events were peripheral neuropathy of any grade (sensory 19/52 [37%]; motor (14/52 [27%]), and cytopenias (grade 3 or 4: (25/52 [48%]), including neutropenia (13/52 [25%]), thrombocytopenia (7/52 [14%]), and anemia (5/52 [10%]). Three patients (6%) experienced infusion-related reactions. The median number of BV cycles completed post-ASCT was 12 (range 1-17), and 16 patients (31%) completed the full 16 cycles of BV. The most common reason for premature termination was adverse effects (22/36 [61%]). Additional reasons included: physician plan for shorter duration (4/36 [11%]), patient/family decision (3/36 [8%]), and progression (1/36 [3%]). Treatment was still ongoing in 3 patients and reason for premature termination was not reported for 17/36 patients (47%). With a median follow of 2.8 years (range 0.1 to 6.25 years) the three-year EFS was 92% [95%CI: 83-100]. Patients with 0-1 risk factors (15/52 [29%]) and ≥ 2 risk factors (37/52 [71%]), had a 3-year EFS of 100% and 90% [95%CI: 79-100], respectively. Fifty patients (96%) are alive with no evidence of disease, while 2 (4%) patients are alive with disease. No deaths have occurred. Conclusion: The use of post-ASCT BV consolidation for pediatric patients with R/R HL is associated with a favorable safety and tolerability profile. In this cohort, the combination of salvage therapy, HD-chemotherapy/ASCT, and BV consolidation resulted in extremely promising outcomes and warrants further investigation in a prospective pediatric trial. Figure 1 Figure 1. Disclosures Leger: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbott Diagnostics: Research Funding. Roth: Merck: Consultancy; Janssen: Consultancy.

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Bi-institutional retrospective cohort study evaluating the incidence of osteosarcoma following tibial plateau levelling osteotomy (2000–2009)

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.3415/vcot-14-01-0006 ◽

2014 ◽

Vol 27 (05) ◽

pp. 339-345 ◽

Cited By ~ 7

Author(s):

A. J. Sartor ◽

S. D. Ryan ◽

T. Sellmeyer ◽

S. J. Withrow ◽

L. E. Selmic

Keyword(s):

Risk Factors ◽

At Risk ◽

Median Time ◽

Tibial Plateau ◽

Cox Regression ◽

Incidence Density ◽

Colorado State University ◽

Potential Risk Factors ◽

Low Incidence

SummaryObjectives: To evaluate the incidence and risk factors for occurrence of osteosarcoma (OSA) following tibial plateau levelling osteotomy (TPLO).Methods: Medical records of client-owned dogs that underwent consecutive TPLO procedures at two institutions were retrospectively reviewed. Referring veterinarians and owners were contacted for follow-up. Each institutional cohort was assessed separately, and the incidence density rate and median time to occurrence of OSA at the TPLO site and at other sites were calculated. Marginal Cox regression was used to calculate hazard ratios and 95% confidence intervals for potential risk factors for occurrence of OSA.Results: There were 472 CLINIC A (Colorado State University Veterinary Teaching Hospital) and 1992 CLINIC B (SAGE Centers for Veterinary Specialty and Emergency Care) TPLO cases with over one year of follow-up available. There were five and six dogs within the cohorts that developed OSA at the site of TPLO, and seven and 22 dogs that developed OSA at other anatomical sites, respectively. The incidence density rates of OSA at the TPLO site were 30.4 and 10.2 per 10,000 dog-years at risk, and other sites were 42.6 and 37.5 per 10,000 dog-years at risk. The median time to occurrence of OSA of TPLO site OSA was 4.6 and 4.4 years, which was longer than that of other site OSA of 2.9 and 3.4 years.Clinical significance: There is a low incidence of OSA following TPLO surgery. The longer time to occurrence for TPLO site OSA is similar to that for fracture-associated sarcoma, and could indicate a similar underlying pathophysiology rather than spontaneous OSA occurrence.

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Outcomes for Patients (Pts) with Low-/Int-1-Risk Myelodysplastic Syndromes (MDS) with del5q Aged < 65 Years Treated with Lenalidomide (LEN) in MDS-003 and MDS-004: A Retrospective Combined Analysis

Blood ◽

10.1182/blood.v118.21.1723.1723 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1723-1723 ◽

Cited By ~ 1

Author(s):

Pierre Fenaux ◽

Aristoteles Giagounidis ◽

Alan F. List ◽

Stephen D. Nimer ◽

Eva Hellström-Lindberg ◽

...

Keyword(s):

Risk Factors ◽

Board Of Directors ◽

Potential Risk ◽

Research Funding ◽

Advisory Committees ◽

Secondary Failure ◽

Potential Risk Factors ◽

Rbc Transfusion ◽

Reduced Risk

Abstract Abstract 1723 Background: Two multicenter studies (MDS-003/-004) found LEN leads to RBC transfusion independence (TI) in > 50% of pts with RBC transfusion dependent Low-/Int-1-risk MDS with del5q (List A et al. NEJM 2006;355: 1456–65; Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). RBC-TI ≥ 8 wks with LEN was associated with significantly reduced risk of AML progression and death (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). Alternative therapy is required for pts failing LEN therapy. Aims: To assess predictive factors of LEN response and long term outcomes (especially after primary or secondary LEN failure) of pts < 65 yrs included in MDS-003/-004; ie, those in whom intensive therapies including allogeneic stem cell transplantation (ASCT) may be considered. Methods: LEN was administered as follows (all 28-d cycles): 5 mg/d on d 1–28 and 10 mg/d on d 1–21 or 1–28. RBC-TI ≥ 26 wks and cytogenetic response (CyR; IWG 2000) are reported. Overall survival (OS) and AML progression were assessed using Kaplan-Meier method. Response rates and outcomes in pts < 65 yrs were retrospectively compared with pts ≥ 65 yrs. Primary failure was defined as lack of RBC-TI with LEN treatment and secondary failure as relapse after achievement of RBC-TI ≥ 26 wks. Cox proportional hazards models were used to evaluate the effect of potential risk factors (ie, age, sex, time since diagnosis, FAB classification, LEN dose, IPSS risk, WPSS risk, cytogenetics, bone marrow blast %, transfusion burden, no. of cytopenias, hemoglobin level, platelet and neutrophil counts, RBC-TI ≥ 26 wks [time-dependent variable] and CyR [categorical variable]) on OS and AML progression. Logistic model was used to evaluate the effect of potential risk factors on achievement of RBC-TI ≥ 26 wks. Results: The trials included 97 (33.9%) pts < 65 yrs. Of these, 73.2% were female; 20.6% were IPSS Low-, 52.6% Int-1-, and 4.1% Int-2-risk; 30.9% had del5q with ≥ 1 additional cytogenetic abnormality (8.2% had complex cytogenetics). At baseline (BL), median time since diagnosis was 2.4 yrs (range 0.2–20.7) and median RBC transfusion requirement was 6 units/8 wks (range 1–15). In pts ≥ 65 yrs (n = 189) most BL characteristics were similar except IPSS risk, which was lower (36.5% Low-, 37.0% Int-1-, 5.8% Int-2-risk; p =.012). RBC-TI ≥ 26 wks was achieved by 54 (55.7%) pts < 65 yrs (vs 49.7% pts ≥ 65 yrs; p =.563). The median duration of RBC-TI ≥ 26 wks in responders was not estimable in pts < 65 yrs or ≥ 65 yrs (log-rank p =.879). None of the potential risk factors assessed was a significant predictor of RBC-TI ≥ 26 wks in pts < 65 yrs, possibly due to small pt number. In pts < 65 yrs with available follow-up cytogenetics (n = 71), CyR was achieved by 32 (45.1%) pts (vs 64.5% pts ≥ 65 yrs; p =.014). At time of data cutoff, 51 (52.6%) pts < 65 yrs were alive (vs 36.0% pts ≥ 65 yrs; p =.008); 29 (29.9%) pts progressed to AML (vs 20.1% pts ≥ 65 yrs; p =.077). The 1-, 2-, and 3-yr AML-progression rates were 9.7%, 15.4%, and 24.0% in pts < 65 yrs; and 6.0%, 17.9%, and 22.3% in pts ≥ 65 yrs (log-rank p =.308). The 1-, 2-, and 3-yr OS rates were 91.7%, 78.1%, and 66.4% in pts < 65 yrs; and 83.1%, 65.2%, and 49.9% in pts ≥ 65 yrs (log-rank p <.001). In pts < 65 yrs, RBC-TI ≥ 26 wks was the only factor associated with longer median OS (4.9 yrs in responders vs 2.0 yrs in non-responders) and lower BL ANC was the only factor associated with a reduced risk of AML-progression. A total of 43 (44.3% of total population) pts < 65 yrs experienced primary LEN failure and 9 (16.7% of responders) secondary failure. In pts < 65 yrs with primary failure after 16 wks (median follow up from primary failure 2.6 yrs), 13 (30.2%) pts progressed to AML (1- and 2-yr cumulative AML rates 7.9% and 16.8%) and median OS was 2.67 yrs. In pts < 65 yrs with secondary failure (median follow up from secondary failure 1.7 yrs), 3 (33.3%) pts progressed to AML and median OS was not reached (1-yr cumulative OS rate was 64.8%). Conclusions: LEN-treated pts < 65 yrs had greater incidence of IPSS Int-1-risk, had similar rates of RBC-TI ≥ 26 wks, but achieved CyR less often and more progressed to AML vs pts ≥ 65 yrs. In pts < 65 yrs, achievement of RBC-TI ≥ 26 wks was the only factor associated with longer OS. After primary or secondary LEN failure, AML progression rates were ∼30% each, and median OS 2.67 yrs and 1-yr OS 64.8%, respectively. Low-/Int-1-risk pts < 65 yrs with del5q and primary or secondary LEN failure have a relatively poor outcome and should be considered potential candidates for ASCT. Disclosures: Fenaux: Celgene Corporation: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Merck: Honoraria; Cephalon: Honoraria; Novartis: Honoraria. Giagounidis:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. List:Celgene Corporation: Consultancy, Honoraria, Research Funding. Hellström-Lindberg:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Yu:Celgene Corporation: Employment, Equity Ownership. Skikne:Celgene Corporation: Employment. Shammo:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. del Cañizo:Celgene Corporation: Spanish advisory committee.

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Treatment-Free Remission (TFR) in Patients with Chronic Phase Chronic Myeloid Leukemia (CML-CP) and in Stable Deep Molecular Response (DMR) to Dasatinib - the Dasfree Study

Blood ◽

10.1182/blood.v128.22.1895.1895 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1895-1895 ◽

Cited By ~ 20

Author(s):

Neil P. Shah ◽

Ronald Paquette ◽

Martin C. Müller ◽

Susanne Saussele ◽

Valentin Garcìa-Gutiérrez ◽

...

Keyword(s):

Board Of Directors ◽

Median Time ◽

Interim Analysis ◽

Research Funding ◽

Molecular Response ◽

Phase 2 ◽

Advisory Committees ◽

Free Survival ◽

Kinetics Of

Abstract Background: Prior clinical trials demonstrated that 33-61% of patients with CML maintain disease control following TKI discontinuation in the 1st line and beyond (Thielen, Eur J Cancer. 2013; Mahon, Lancet Oncol. 2010; Hochhaus, ASCO 2016; Hughes, ASCO 2016; Imagawa, Lancet Haematol. 2015). Patients who relapsed after discontinuation regained major molecular response (MMR) upon retreatment. Dasatinib, a 2nd generation TKI, induces fast and deep molecular responses, making it an effective option for patients in view of a possible TFR. Here, we report interim results from the phase 2 DASFREE study, investigating TFR with dasatinib in the 1st and 2nd line settings. Methods: DASFREE (CA180-406/NCT01850004) is a phase 2 open-label, single-arm study in adults with CML-CP who were on dasatinib for ≥2 yr as 1st line or subsequent therapy, had confirmed dasatinib-induced DMR (defined as MR4.5, BCR-ABL1 ≤0.0032% [IS]) for ≥1 yr prior to enrollment, and achieved a 1-log reduction in BCR-ABL1 from baseline within 3-6.5 mo of starting dasatinib. Prescreening for MR4.5 was done at a local lab, with confirmation at a central lab twice over a 3-mo interval prior to dasatinib discontinuation (screening phase). BCR-ABL1 was monitored centrally after treatment discontinuation every mo in the 1st yr, then every 3 mo. If loss of MMR occurred, patients resumed dasatinib at the previous dose. The primary endpoint is MMR rate at 1 yr after dasatinib discontinuation. Secondary endpoints include kinetics of loss of response, event-free survival (EFS; no loss of MMR), relapse-free survival (RFS; no loss of MMR, complete cytogenetic response, or complete hematologic response, or progression to accelerated/blast phase CML), progression-free survival, and overall survival. Exploratory analyses include frequency of adverse events (AEs) after discontinuation and during dasatinib treatment, and molecular response rates after reinitiating dasatinib. All patients will be followed for up to 5 yr. This analysis reflects a planned interim assessment of patients followed for TFR for ≥1 yr. Results: Currently, 71 patients are enrolled out of 79 planned. Thirty patients (14 male; median age 51 yr [range: 29-76]; Sokal scores: 60% low, 27% intermediate, 3% high, 10% unknown) followed for ≥1 yr after dasatinib discontinuation were included in this interim analysis. MMR rate at 1 yr following discontinuation was 63% (95% CI: 46-81). EFS rate at 1 yr following discontinuation was 63% (95% CI: 44-78; Figure). RFS rate at 1 yr following discontinuation will be presented. Eleven of 30 patients lost MMR, with a median time to loss of MMR of 4 mo (range: 1-8). Median time on dasatinib prior to discontinuation was 40 mo (range: 26-114) for patients who lost MMR and 55 mo (range: 31-87) for patients who retained MMR. Eleven patients who lost MMR restarted dasatinib therapy: 10 regained MMR, and 1 patient chose to restart therapy at a nonstudy site, discontinued study, and was lost to follow-up. The kinetics of molecular relapse, the number of patients that regained DMR, and the time to regain MMR or DMR will be presented. No transformation events or deaths were observed at the time of this analysis. After discontinuation, 5 patients had musculoskeletal AEs; in 2 patients (with 3 events) these AEs were attributed to withdrawal from dasatinib by investigators. Additional AEs following discontinuation included hypertension (17%) and skin disorders (13%). For patients who restarted dasatinib, AEs were consistent with the known safety profile, and none of the on-treatment AEs resulted in discontinuation. Conclusions: This interim analysis of the first 30 patients enrolled in DASFREE demonstrated patients with dasatinib-induced DMR treated in the 1st and 2nd line had high rates of success at maintaining remission after treatment was discontinued (63% MMR and EFS at 1 yr), and there was rescue of molecular response in all patients once dasatinib was reinitiated. There is a suggested correlation between time on dasatinib prior to discontinuation and maintaining MMR. Dasatinib withdrawal appears to be tolerable, as there was a low incidence of withdrawal symptoms. These data build upon the growing body of evidence supporting the feasibility of TFR in patients with CML-CP and demonstrate that with frequent monitoring of BCR-ABL1, patients treated with dasatinib in the 1st and 2nd line can successfully discontinue treatment. Longer-term follow-up is ongoing. Figure Figure. Disclosures Shah: Bristol-Myers Squibb, ARIAD, Pfizer, Daiichi-Sankyo, Plexxikon: Research Funding. Paquette:Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Ariad: Research Funding, Speakers Bureau. Müller:Ariad, BMS, Novartis, Pfizer: Honoraria; Ariad, BMS, Novartis, Pfizer: Consultancy; Institute for Hematology and Oncology, IHO GmbH: Employment, Equity Ownership. Saussele:Novartis, BMS, Ariad, Pfizer: Honoraria; Novartis, BMS: Research Funding. Garcìa-Gutiérrez:Novartis, BMS, Ariad and Pfizer: Consultancy; Novartis, BMS, Ariad and Pfizer: Research Funding. Nicolini:Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria. Mauro:ARIAD: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Mahon:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Ariad: Honoraria. Rea:Novartis: Honoraria; Ariad: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Martin-Regueira:Bristol-Myers Squibb: Employment. Subar:Bristol Myers-Squibb: Employment. Li:Bristol-Myers Squibb: Employment. Lipton:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

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Trend and treatment outcomes of latent tuberculosis infection among migrant persons in Japan: retrospective analysis of Japan tuberculosis surveillance data

BMC Infectious Diseases ◽

10.1186/s12879-020-05712-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lisa Kawatsu ◽

Kazuhiro Uchimura ◽

Akihiro Ohkado

Keyword(s):

Risk Factors ◽

Surveillance System ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Migrant Population ◽

Foreign Born ◽

Ltbi Treatment ◽

Potential Risk Factors ◽

Lost To Follow Up

Abstract Background Screening for latent tuberculosis infection (LTBI) among migrant population has become a critical issue for many low tuberculosis (TB) burden countries. Evidence regarding effectiveness of LTBI programs are limited, however, partly because of paucity of national data on treatment outcomes for LTBI. In Japan, notification of LTBI is mandatory, and its treatment outcome is reported as part of Japan’s national TB surveillance system. We thus conducted a detailed analysis of LTBI among foreign-born persons, to update the epidemiological trend of newly notified LTBI between 2007 and 2018, and to examine the treatment regimen and outcome of those notified in 2016 and 2017, focusing specifically on the potential risk factors for lost to follow-up. Methods We extracted and analyzed the data of newly notified LTBI patients from the Japan Tuberculosis Surveillance System to examine the overall trend of notification and by age groups and modes of detection between 2007 and 2018, and the cohort data for treatment regimen and outcomes of foreign-born persons notified with LTBI in 2016 and 2017. Trends and proportions were summarized descriptively, and logistic regression analysis was conducted to identify potential risk factors for lost to follow-up. Comparisons were made with the Japan-born patients where appropriate, using chi-squared tests. Results Both the number and proportion of LTBI among foreign-born persons have been constantly increasing, reaching 963 cases in 2018. Cohort analysis of the surveillance data indicated that the proportion of those on shorter regimen was higher among the foreign- than Japan-born patients (5.5% vs. 1.8%, p < 0.001). The proportion of those who have been lost to follow-up and transferred outside of Japan combined was higher among the foreign- than Japan-born patients (12.0% vs, 8.2%, p < 0.001). Risk factors for lost to follow-up were being employed on a temporal basis, and job status unknown (adjusted odds ratios 3.11 and 4.09, 95% confidence intervals 1.34–7.26 and 1.60–10.48, respectively). Conclusions Migrant population face greater risk of interrupting LTBI treatment, and interventions to improve adherence are a critical component of programmatic management of LTBI. Further studies are needed to explore the cultural and socioeconomic situation in which foreign-born persons undergo LTBI treatment in Japan.

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