Citations

Abstract Background: Isatuximab (ISA) is an anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells through immune cell engagement and direct tumor targeting. In preclinical studies, pomalidomide (Pom) enhanced both the direct and indirect anti-tumor activity of ISA to a greater degree than lenalidomide (Len) (Jiang et al. Leukemia 2016). Here, we report the preliminary results of an ongoing Phase Ib dose-escalation study of ISA plus Pom and dexamethasone (Dex) in patients with relapsed and refractory multiple myeloma (RRMM) (NCT02283775). Methods: Patients with RRMM (≥2 prior MM therapies, including Len and a proteasome inhibitor) with adequate bone marrow reserve/organ function were sequentially enrolled to receive ISA 5, 10 or 20 mg/kg (weekly × 4 doses, then every 2 weeks until disease progression or intolerable toxicity) in combination with Pom 4 mg (days 1-21) and Dex 40 mg (days 1, 8, 15, and 22; 20 mg if ≥75 years old), in 28-day cycles. Pom or Dex dose reductions were permitted after Cycle 1, or during Cycle 1 in response to dose-limiting toxicities (DLTs). The primary objective was to determine the maximum tolerated dose (MTD) or recommended dose, based on the occurrence of treatment-related DLTs. Secondary objectives included evaluation of efficacy (by objective response assessment according to IMWG criteria), safety, and pharmacokinetics (PK). Results: At data cut-off (May 11, 2016), 14 patients had been treated in the first 2 dose-escalation cohorts: 8 patients at 5 mg/kg and 6 patients at 10 mg/kg. Overall, median age was 65.5 (range, 42-77) years and median time from diagnosis was 4.25 (1.0-12.5) years. Half of the patients (7/14) had received at least 5 prior regimens (median 4.5 [2-11]; prior carfilzomib in 50% of patients). Ten patients (71%) had received at least one prior stem cell transplant. Median duration of dosing was 21.2 (4-42) and 8.1 (4-12) weeks in the 5 mg/kg and 10 mg/kg cohorts, respectively, with the latter cohort also having the shortest follow-up. Three patients discontinued treatment, all in the 5 mg/kg cohort: 2 due to confirmed disease progression (discontinuation after 2 and 4 treatment cycles, respectively) and 1 due to patient withdrawal (discontinuation in Cycle 1 and patient not evaluable for response). There were no discontinuations due to treatment-emergent adverse events (TEAEs) in either cohort. Two DLTs were reported: one in the 5 mg/kg cohort (prolonged grade [Gr] 4 neutropenia), and the other in the 10 mg/kg cohort (Gr 4 neutropenic infection); both DLTs resolved with Pom dose delay/reduction. MTD has not yet been reached; the 20 mg/kg dose level is under enrollment. Overall, Gr 3/4 TEAEs were reported in 10 (71%) patients; serious TEAEs in 6 (43%) patients. The most frequent TEAEs were fatigue (64%), upper respiratory tract infection, tremor, dyspnea, and cough (29% each). The most common Gr 3/4 hematologic abnormality (laboratory assessment) was neutropenia (Gr 1, 0%; Gr 2, 7%; Gr 3, 43%; Gr 4, 43%). Gr 3/4 thrombocytopenia was reported in 4 (29%) patients (Gr 3, n=2; Gr 4, n=2). Infusion-associated reactions (IARs) occurred in 8 (57%) patients, with all cases Gr 1/2 in severity. IARs occurred during the first infusion in most patients; 3/14 (21%) patients experienced IARs at a subsequent infusion, of whom only one had IARs after Cycle 1. Of the patients evaluable for confirmed response, 8/13 (62%) achieved at least partial response (PR), and 10/13 (77%) at least minimal response (MR). At 5 mg/kg, 1 patient achieved complete response (CR), 2 very good partial response (VGPR) and 2 PR. At 10 mg/kg, 2 patients achieved VGPR, 1 PR, and 2 MR. Of the eight patients who achieved at least PR, all continued to respond without confirmed disease progression at data cut-off. The PK parameters of ISA were not affected by co-administration with Pom/Dex. Conclusions: These preliminary data suggest that the combination of ISA and Pom/Dex is generally well tolerated and clinically active in patients with heavily pre-treated RRMM. Enrollment continues and longer term follow-up from this study, including data from the 20 mg/kg cohort, will be presented. A Phase III trial to evaluate ISA plus Pom/Dex is planned. Disclosures Richardson: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mikhael:Sanofi: Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Onyx: Research Funding. Usmani:Pharmacyclics: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Array: Research Funding; Novartis: Speakers Bureau. Raje:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Eli Lilly: Research Funding. Bensinger:Takeda: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Acetylon: Research Funding; Bayer: Research Funding. Campana:Sanofi: Employment. Gao:Sanofi: Employment. Dubin:Sanofi Oncology: Employment. Wack:Sanofi: Employment. Anderson:Gilead: Membership on an entity's Board of Directors or advisory committees; Oncoprep: Equity Ownership; Oncoprep: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Equity Ownership; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Equity Ownership; Acetylon: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Equity Ownership; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

Abstract BACKGROUND: The introduction of novel agents and proteasome inhibitors, and advances in high dose therapy administration has made an impact on the survival outcomes for MM patients. However, HRMM still remains a therapeutic challenge with poor prognosis. Even with aggressive approaches such as the Total Therapy protocols, patients with poor genomic risk have a 2-year event-free survival of ~50% (Nair et al, Blood 2010). A randomized Phase I/II trial was designed to evaluate the efficacy of adding immunotherapy into the first line for HRMM patients, comparing lenalidomide, bortezomib and dexamethasone (RVD) with or without addition of elotuzumab (Elo), a humanized monoclonal antibody that binds to SLAMF7/CS1. We are reporting on the Phase I portion of the study. PATIENTS & METHODS: The objective of Phase I was to determine the maximum tolerated dose (MTD) of RVD-Elo. Both low/standard risk MM and HRMM patients were eligible. HRMM was defined by one or more of the following: (1) poor risk genomics by the Arkansas 70-gene model, (2) translocation (14;16), translocation (14;20) and/or deletion (17p) by florescent in-situ hybridization (FISH), (3) primary plasma cell leukemia and (4) serum LDH > 2 times normal levels. The treatment consisted of induction chemotherapy for 8 cycles with RVD-Elo (lenalidomide 25 mg orally days 1-14 of every 21-day cycle; bortezomib 1.3 mg/m2 subcutaneously days 1,4,8,11; dexamethasone 20 mg orally days 1,2,4,5,8,9,11,12; elotuzumab 10 mg/kg intravenously days 1,8,15 cycles 1-2 then days 1,11 cycles 3-8) followed by dose-attenuated RVD-Elo maintenance (lenalidomide 25 mg orally days 1-14; bortezomib 1.0 mg/m2 subcutaneously days 1,8,15; dexamethasone 12 mg orally days 1,8,15; elotuzumab 10 mg/kg intravenously days 1,15) until disease relapse, progression or intolerance. Adverse events (AE) were recorded as per the NCI CTCAEv4.0. RESULTS: Eight newly diagnosed MM patients were enrolled on the Phase I run-in study. Six patients (Figure 1) were evaluable for dose limiting toxicities (DLT) during Cycle 1 as per protocol. The median age of patients was 67 years (range: 56-79 years), with 67% ≥65 years, Hgb was less than 10 g/dL in 50%, creatinine was greater than 2 mg/dL in all patients. ISS stage distribution was 17% (I), 33% (II) and 50% (III). Deletion 13 was observed in 1 patient (17%). The most common AEs (all grades) were fatigue (100%), peripheral sensory neuropathy (83%), edema (83%), lymphopenia (66%) and leukopenia (50%). The most common Grade 3 AEs were peripheral sensory neuropathy (33%), one of which was a DLT, neutropenia (17%) and thrombocytopenia (17%). One Grade 4 lymphopenia was observed. All 6 patients have completed 8 cycles of RVD-Elo induction therapy and 5 patients have completed at least 4 cycles of RVD-Elo maintenance. Overall median days on therapy per cycle were 13 days during induction and 20 days per cycle during maintenance. Dose adjustments were made in 83% of patients for bortezomib, 83% for lenalidomide and 33% for dexamethasone. There were no dose reductions for elotuzumab, although three patients had 1 event each of dose delays/missed dosing attributable to AE/SAE from RVD. Efficacy data will be released at the time that the phase II study of RVD +/- Elo is mature. Discussion/Conclusion: The RVD-Elo is a safe well-tolerated regimen for newly diagnosed MM patients without major additive AE/SAE beyond what is already known about RVD. This is the first report of the only phase I experience combining the triple-drug regimen RVD with the monoclonal antibody Elotuzumab for newly diagnosed MM. Support: NCI grants CA32102, CA38926, CA180821, CA31946, CA21076, CA180799, CA21115, CA180820 and in part by Bristol-Myers Squibb Company Disclosures Usmani: Celgene Corporation: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Array BioPharma: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma patients. Ailawadhi:Millennium: Honoraria. Shah:Onyx Pharmaceuticals: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Array: Consultancy, Research Funding. Rosenzweig:Celgene: Speakers Bureau. Durie:IRC J&J: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees. Orlowski:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum Pharmaceuticals: Research Funding; JW Pharmaceutical: Research Funding; Array BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Abstract Abstract 4217 Background: AHCT improves survival (OS) in newly diagnosed MM patients (pts) in large randomized trials. These trials have limited eligibility to younger, healthier pts. Selection of older pts and those with co-morbid illness for AHCT is problematic. HCT-CI, originally developed as predictor of post-allogeneic transplant outcomes, maybe valuable in stratifying risk of transplant related mortality (TRM) risk and OS in the AHCT setting. We investigated the relative impact of HCT CI along with other patient and MM related variables on outcomes after AHCT in a large cohort of transplant recipients. Methods: Outcomes of 1156 MM pts receiving AHCT after high dose Melphalan (MEL) between 2007 and 2010 reported to the CIBMTR (Center for International Blood and Marrow Transplant Research) were analyzed. HCTCI scores and individual comorbidities were prospectively reported at time of AHCT. Median follow up of survivors was 26 month. The impact of HCTCI and other potential prognostic factors including Karnofsky performance status (KPS) on OS were studied in multivariate Cox regression models. Results: HCTCI score was 0, 1, 2, 3, >3 in 42%, 18%, 13%, 13% and 14% respectively. Most common co-morbidities included pulmonary, diabetes, obesity, psychiatric, cardiac, renal and prior solid tumor. Using consolidated HCTCI scores, patients were stratified initially into 3 risk groups – HCTCI 0 (42%) vs. HCTCI 1–2 (32%) vs. HCTCI >2 (26%). Males and Caucasians were more likely to have greater HCTCI score. Higher HCTCI was associated with lower KPS <90 (33% in HCTCI 0 cohort vs. 50% in HCTCI >2). HCTCI score >2 was associated with MEL dose reduction to 140 mg/m2 (22% vs. 10% in score 0 cohort). Cytogenetic risk and MM related factors were not correlated with HCTCI. TRM at 12 month was 2%, 2%, and 3% for 3 risk groups. With extremely few TRM events, multivariate analysis did not suggest an impact of HCTCI. OS was 95%, 92%, 92% at 1 year and 87%, 81%, 80% at 2 year, respectively. OS was inferior for HCTCI >2 cohort (RR of death 1.48, p=0.02) and HCTCI cohort 1–2 (RR 1.37, p=0.04) compared with HCTCI 0 cohort. There was no significant difference in OS between HCTCI >2 vs. HCTCI 1–2 (p=0.64). Therefore the latter 2 groups were combined as the HCTCI >0 cohort [N=667] and compared with HCTCI=0 [N=489] in multivariate models. HCTCI >0 predicted inferior OS (RR of death= 1.41, p=0.01). Other significant predictors of inferior survival were KPS <90 (RR of death 1.61, p<0.01), IgA subtype (RR 1.64, p<0.01), >1 pretransplant regimen (RR 1.47, p<0.01), resistant MM at AHCT (RR 1.78, p<0.01). Major cause of death in both groups was progressive MM. Conclusion: In clinical practice, higher HCTCI score was associated with MEL dose reduction. Mortality after AHCT is predominantly related to MM progression/relapse with low incidence of TRM. Higher HCTCI scores were independently associated with inferior OS. KPS remains an important tool for risk stratification. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction Lenalidomide-based therapies are a standard of care for patients with newly diagnosed, transplant-ineligible MM. Daratumumab (DARA) is a human, CD38-targeted, IgG1κ monoclonal antibody which has single-agent activity in heavily pretreated MM patients. As previously reported in 3 phase 3 studies, the addition of DARA to standards of care in both relapsed refractory (D-Rd, DARA plus bortezomib and dexamethasone [D-Vd]) or transplant-ineligible NDMM (DARA plus bortezomib, melphalan, and prednisone [D-VMP]) resulted in a ≥50% reduction in the risk of disease progression or death (Palumbo A, et al. N Engl J Med 2016;375:754-766; Dimopoulos MA, et al. N Engl J Med 2016;375:1319-1331; Mateos MV, et al. N Engl J Med 2018;378:518-528). Of these, the POLLUX study with D-Rd showed the greatest benefit with a 63% reduction in risk of disease progression or death in patients with MM who had at least one prior line of therapy. Based on the efficacy and tolerable safety profile of D-Rd, we conducted a phase 3 study (MAIA) to evaluate D-Rd vs Rd in transplant-ineligible NDMM. Here we report the prespecified interim analysis of the MAIA study. Methods Patients ineligible for high-dose chemotherapy with autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to Rd ± DARA. Stratification was based on International Staging System stage (ISS [I, II, III]), region (North America vs other), and age (<75 vs ≥75 years). All patients received 28-day cycles of treatment with Rd ± DARA. R: 25 mg (oral) QD on Days 1-21; d: 40 mg (oral) on Days 1, 8, 15 and 22. In the D-Rd arm, DARA was given at 16 mg/kg (intravenously) QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. In both arms, patients were treated until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), minimal residual disease (MRD)-negativity rate (10-5 sensitivity, clonoSEQ® version 2.0), and safety. Results This international study randomized 737 patients (368 to D-Rd; 369 to Rd) from 14 countries. Key baseline characteristics were well balanced between the two arms. The median (range) age was 73 (45-90) years with 44% of patients ≥75 years, and 52% were male. Two thirds of patients had ECOG scores ≥1: ECOG score 0, 34%; 1, 50%; ≥2, 17%. Overall, 27%, 43%, and 29% were ISS stage I, II, and III, respectively. Of 642 patients evaluable for FISH/karyotyping analysis, 86% and 14% were standard and high cytogenetic risk, respectively. The prespecified interim analysis occurred after 239 PFS events on 24 September 2018 with a median follow up of 28 months. For the primary endpoint, the hazard ratio was 0.55 (95% CI, 0.43 to 0.72; P <0.0001), representing a 45% reduction in the risk of progression or death in patients treated with D-Rd (Figure). The median PFS for the Rd arm was 31.9 months and not reached for the D-Rd arm. Adding DARA to Rd resulted in deeper responses with a complete response (CR) or better rate of 47.6% in the D-Rd arm compared with 24.7% in the Rd arm (odds ratio [OR] 2.75, 95% CI, 2.01 to 3.76; P <0.0001). The very good partial response (VGPR) or better rate was 79.3% in the D-Rd arm compared with 53.1% in the Rd arm (OR 3.4, 95% CI, 2.45 to 4.72; P <0.0001). A total of 19% of patients have died and the HR for OS was 0.78 (95% CI, 0.56 to 1.1); follow-up is ongoing. Higher rates (5% or more difference) of grade 3/4 pneumonia, neutropenia, and leukopenia were observed in the D-Rd arm. The safety profile is consistent with previously reported DARA studies. The complete topline data set will be presented with additional efficacy endpoints, including MRD negativity rate. Conclusion The addition of DARA to Rd in patients with transplant-ineligible NDMM significantly reduced the risk of progression or death by 45%. There are no new safety signals using DARA plus Rd in NDMM. These data together with the phase 3 ALCYONE study (D-VMP vs VMP) support the addition of DARA to standard of care combinations in patients with NDMM ineligible for transplant. Disclosures Facon: Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Plesner:Celgene: Other: Independent Response Assessment Comittee; Janssen: Consultancy. Orlowski:Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioTheryX: Research Funding; Spectrum Pharma: Research Funding. Moreau:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bahlis:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Hulin:Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Research Funding. Goldschmidt:Adaptive Biotechnology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; ArtTempi: Honoraria. O'Dwyer:Janssen: Consultancy. Perrot:Janssen: Consultancy, Equity Ownership, Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Weisel:Celgene: Consultancy; Angeb: Consultancy, Honoraria, Research Funding; Juno: Consultancy; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Research Funding; Bristol Myers SquibbMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Ahmadi:Genmab: Employment, Equity Ownership. Chiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Wang:Janssen Research & Development, LLC: Employment. Van Rampelbergh:Janssen: Employment. Uhlar:Janssen: Employment. Kobos:Janssen Research & Development: Employment. Qi:Janssen Research & Development, LLC: Employment. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding.

Abstract Objectives: Infection with the causative agent of visceral leishmaniasis (VL) may be either symptomatic or asymptomatic. In this study we aimed at investigating the prevalence of asymptomatic infections of leishmania in non-endemic villages in Gedaref state, Sudan. A descriptive cross-sectional study conducted during September and October 2014. Blood samples were collected for serological and molecular analysis. Sticky-traps, knockdown spray and CDC-miniature light traps were used for the collection of sandflies. Results: Ninety-Five participants were included; 52 from Abukishma, 15 Algadamblia Tirfa, 25 Abualnaja and 3 were from Algadamblia Aljabal . Females constituted 56 (58.9%) of the study participants while males were 39 (41.1%). The most frequent age group was >40-years (54.7%). Balanites/Acacia trees were the most planted tree inside the houses; 78 (82.1%). Also, 85 (89.5%) of the participants breed animals inside the house. DAT test revealed 5 positive participants (5.2%). 4/5 DAT positive were past VL infection. PCR detected 35 (36.8%) positive participants. A total of 31/35 was considered asymptomatic infections based on PCR. Households planted Balanites/Acacia trees or breed domestic animals were found in high percentages with L. donovani PCR positive participants (60.1%, 91.4%). No statistically significant was found for VL associated risk factors and VL asymptomatic participants.

Abstract Objectives: Infection with the causative agent of visceral leishmaniasis (VL) may be either symptomatic or asymptomatic. In this study we aimed at investigating the prevalence of asymptomatic infections of leishmania in non-endemic villages in Gedaref state, Sudan. A descriptive cross-sectional study conducted during September and October 2014. Blood samples were collected for serological and molecular analysis. Sticky-traps, knockdown spray and CDC-miniature light traps were used for the collection of sandflies. Results: Ninety-Five participants were included; 52 from Abukishma, 15 Algadamblia Tirfa, 25 Abualnaja and 3 were from Algadamblia Aljabal . Females constituted 56 (58.9%) of the study participants while males were 39 (41.1%). The most frequent age group was >40-years (54.7%). Balanites/Acacia trees were the most planted tree inside the houses; 78 (82.1%). Also, 85 (89.5%) of the participants breed animals inside the house. DAT test revealed 5 positive participants (5.2%). 4/5 DAT positive were past VL infection. PCR detected 35 (36.8%) positive participants. A total of 31/35 was considered asymptomatic infections based on PCR. Households planted Balanites/Acacia trees or breed domestic animals were found in high percentages with L. donovani PCR positive participants (60.1%, 91.4%). No statistically significant was found for VL associated risk factors and VL asymptomatic participants.

Abstract Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, &lt;1-99 days]; RIC/NMA, 21 days [range, &lt;1-100 days]; P &lt; .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P &lt; .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P &lt; .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.