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Chimeric antigen receptor T-cell (CAR-T) therapy is standard-of-care in relapse/refractory aggressive B-cell non-Hodgkin lymphoma. There are limited data regarding the impact of pre-existing chronic kidney disease (CKD) and acute kidney injury (AKI) post CAR-T and we sought to evaluate these in our patients.In this single center retrospective analysis CKD cohort was defined KDIGO staging with eGFR of60 mL/min/1.73 m2 (Stage ...3) at the time of pre-CAR-T assessment. Remaining patients constituted the no CKD group. AKI was defined by CTCAEv.4 and data were abstracted through Day 100 post-CAR-T therapy. The primary outcome was impact of pre-existing CKD on progression-free survival (PFS), overall survival (OS) and adverse events. Additionally, we also analyzed the impact of AKI on PFS and OS.Thirty-two patients were identified with 7 having pre-existing CKD. Among the patients with or without CKD, the median PFS was 8.8 and 2.9 months respectively (pvalue 0.78). The median OS was 10 and 7 months respectively (p-value 0.64). AKI developed in a total of 9 patients (29%) post CAR-T, including 7 patients without CKD at baseline. The median PFS was 3.6 and 2.8 months for patients not developing AKI and developing AKI (p-value 0.84). Median OS in similar order was 10 and 3.9 months respectively (p-value 0.2). On univariate analysis, creatinine at baseline (p-value 0.018) and ICANS grade 2+ (p-value 0.016) were associated with an increased risk of developing AKI.CKD or AKI after CAR-T showed no impact on post procedure OS and PFS.

Management of secondary central nervous system (SCNS) involvement in relapsed or refractory aggressive B-cell lymphomas remains an area of unmet medical need. We report a single-center retrospective analysis of 7 adult patients with SCNS lymphoma (SCNSL) who underwent chimeric antigen receptor (CAR) T-cell therapy for their refractory disease, and we describe the safety of whole brain radiation therapy (WBRT) as a bridging therapy. Six patients (85.7%) achieved a complete response at day 28, and 1 patient had progressive disease. The median progression-free survival was 83 days (range, 28-219 days), and median overall survival was 129 days (range, 32-219 days). Three patients died as a result of disease progression. Of the 5 patients who received WBRT as bridging therapy, 3 had no immune effector cell–associated neurotoxicity syndrome (ICANS), but 2 patients had grade 1 or grade 3 ICANS. No grade 4 ICANS was reported in this subset of patients. We conclude that SCNSL should not preclude patients from receiving CAR T-cell therapy as a treatment option because of concerns regarding ICANS, and bridging with WBRT is not associated with increased ICANS., Key Points SCNSL should not preclude patients from receiving CAR T-cell therapy because of concerns regarding ICANS.WBRT is not associated with increased ICANS when used as a bridge to CAR T-cell therapy with a short median interval in SCNSL.

Improved biomarkers are needed to guide the optimal use of autologous stem cell transplantation (ASCT) for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples or post-ASCT peripheral blood mononuclear cell (PBMC) and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, p

BACKGROUND: Right ventricular failure is an underrecognized consequence of COVID-19 pneumonia. Those with severe disease are treated with extracorporeal membrane oxygenation (ECMO) but with poor outcomes. Concomitant right ventricular assist device (RVAD) may be beneficial. METHODS: A retrospective analysis of intensive care unit patients admitted with COVID-19 ARDS (Acute Respiratory Distress Syndrome) was performed. Nonintubated patients, those with acute kidney injury, and age > 75 were excluded. Patients who underwent RVAD/ECMO support were compared with those managed via invasive mechanical ventilation (IMV) alone. The primary outcome was in-hospital mortality. Secondary outcomes included 30-d mortality, acute kidney injury, length of ICU stay, and duration of mechanical ventilation. RESULTS: A total of 145 patients were admitted to the ICU with COVID-19. Thirty-nine patients met inclusion criteria. Of these, 21 received IMV, and 18 received RVAD/ECMO. In-hospital (52.4 versus 11.1%, P = 0.008) and 30-d mortality (42.9 versus 5.6%, P= 0.011) were significantly lower in patients treated with RVAD/ECMO. Acute kidney injury occurred in 15 (71.4%) patients in the IMV group and zero RVAD/ECMO patients (P< 0.001). ICU (11.5 versus 21 d, P= 0.067) and hospital (14 versus 25.5 d, P = 0.054) length of stay were not significantly different. There were no RVAD/ECMO device complications. The duration of mechanical ventilation was not significantly different (10 versus 5 d, P = 0.44). CONCLUSIONS: RVAD support at the time of ECMO initiation resulted in the no secondary end-organ damage and higher in-hospital and 30-d survival versus IMV in specially selected patients with severe COVID-19 ARDS. Management of severe COVID-19 ARDS should prioritize right ventricular support.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Cutaneous metastasis from colon cancer is rare, occurs in less than 6% of patients and its associated with poor prognosis. Most often it presents in the abdomen, inguinal or perineal regions, supraclavicular area, and less commonly on the face, neck, scalp, and prior surgical sites. We present a case of a 41-year-old female with colon cancer who developed cutaneous metastases to the scalp, and was treated with topical 5-FU and radiation therapy. Treatment options for cutaneous metastases usually include systemic therapy, topical chemotherapy, surgical excision, or radiation. Our case is probably the first report who was treated with topical 5-FU in addition to radiation therapy. This treatment modality is easy to use and we would recommend clinical trials to be conducted to further study the use of topical 5-FU.

754 Background: ATM and CHEK2 mutations are linked to homologous recombination DNA repair deficiency, with the potential for improved therapeutic response to DNA damaging agents. To investigate our clinical observation of improved outcomes with irinotecan (IRI) based chemotherapy in advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) patients (pts) with somatic or germline ATM/ CHEK2 mutations, we examined our institutional real world experience. Methods: Between 2015-2021, 33 pts with ATM or CHEK2 mutations treated with chemotherapy were identified, of which 16 pts had advanced/metastatic disease. Progression-free survival (PFS) was calculated and compared (Kaplan Meier, log-rank test) in several ways to assess the impact of IRI vs platinum or other regimens. The event for PFS was progression (or death), and pts without progression were censored at treatment end, or at last follow up if treatment was ongoing. Results: Among 16 pts with advanced/metastatic PDAC, 8 (50%) had ATM (5 germline, 3 somatic) and 8 (50%), CHEK2 alterations (4 germline, 4 somatic). Overall, pts received 48 lines of chemotherapy (platinum-based-(No-IRI) N=14; IRI-based-(No-Platinum) N=8; both N=4; none N=22). For best-PFS among pts analysis, median line of best-PFS therapy for IRI-Ever (N=9 pts) was 2nd line (range 1-7) and for IRI-Never (N=7 pts) was 1st (range, 1-1); median PFS was 13 vs 3 months (mo) (IRI-Ever vs IRI-Never; p=0.0076). For PFS analysis within lines of treatment of each pt, median therapy line for both IRI-containing and No-IRI lines was 2nd line (range 1-7); median PFS for IRI-containing (N=12 lines of therapy) vs No-IRI (N=36) was 12.1 vs 3 mo (p

783 Background: Duodenal adenocarcinomas (DA) and ampullary adenocarcinoma (AA) are rare, comprising less than 1% of all gastrointestinal cancers. Optimal treatment sequencing strategies for patients with localized DA and AA have not been prospectively validated. We analyzed the clinical outcomes of patients with localized DA and AA treated with curative intent, multimodality therapy based on treatment sequencing – upfront surgery versus neoadjuvant therapy. Methods: Our institutional database was interrogated to identify adult patients with localized DA and AA diagnosed between January 2000 to December 2019. Adjusted survival analyses were performed to compare outcomes of patients that received neoadjuvant therapy (NAT - concurrent chemo-radiation +/-induction chemotherapy) versus upfront surgery (+/- adjuvant chemotherapy). Survival time was calculated from date of diagnosis to either death (overall survival; OS) or relapse/death (relapse free survival; RFS). Log-rank test and multiple Cox proportional hazards regression were performed to compare survival between treatment groups and adjust for relevant variables. Results: We identified 79 patients – 32 (41%) with DA and 47 (59%) with AA; Median age at diagnosis was 67. Forty two patients (53%) were male. Sixty-two patients underwent surgery – 27 (43.6%) patients with DA and 35 patients (56.4%) with AA. Among patients with DA, 18 (67%) were treated with upfront surgery, while 9 (33%) were treated with NAT. Among patients with AA, 32 (91%) were treated with upfront surgery while 3 (9%) were treated with NAT. Lymph node (LN) positivity rate in DA and AA patients treated with upfront surgery was 15% and 46% respectively, compared to 50% and 0% respectively, in patients treated with NAT (p = 0.26, p > 0.99 respectively). DA patients treated with upfront surgery had a median relapse free survival (mRFS) of 3.8 years compared to 1.4 years for those treated with NAT (p = 0.370). The median overall survival m(OS) was not reached (NR) for DA patients treated with upfront surgery (4 years +) or NAT (2.6 years +) p = 0.875). AA patients treated with upfront surgery had a median RFS of 4.7 years compared to NR for patients treated with NAT (p = 0.117) while the mOS of AA patients treated with upfront surgery and NAT were 5.9 years and NR respectively (p = 0.158). Conclusions: Among DA patients, there was no difference in outcome based on sequence of treatment delivery – NAT versus upfront surgery. DA patients with more aggressive clinical phenotype were likely treated with NAT, hence similar outcomes in both groups should prompt consideration of NAT for all patients with DA. Role of NAT in AA is not clear considering the small sample size.

Clinical relapses early after autologous stem cell transplantation portrays an inferior clinical outcome. Early relapse in this setting with extramedullary disease (EMD) of lung involvement in multiple myeloma is rare. To our knowledge, this is the first reported case of lymphangitic spread of myeloma with pulmonary parenchymal and pleural involvement occurring at first relapse.

e16260 Background: Therapeutic inhibition of constitutive signaling mediated by mutated KRAS in PDAC remains a challenge except for modest success reported with KRAS G12C inhibition. A combinatorial strategy utilizing simultaneous MEK and autophagy inhibition holds therapeutic promise based on mechanism of action and preclinical data. We described characteristics and outcomes of patients (pts) treated with MEK-inh and HCQ at our institution. Methods: Ten KRAS-mutated advanced PDAC pts were treated with trametinib-HCQ (n = 9) or cobimetinib-HCQ (n = 1) off label due to lack of standard treatment options or toxicity concerns with cytotoxic systemic therapy. Trametinib dose was 2 mg once daily orally, Cobimetinib dose was 20 mg BID orally for 3/4 weeks cycles. HCQ was started at 200 mg BID and up-titrated weekly to 600 mg BID. Description of baseline and treatment (tx) characteristics, safety and efficacy is provided. Results: Median age at diagnosis was 61.3 years, and 7 pts were female. The number of prior lines of tx were 0/1/2/3/4 in 3/2/1/2/2 pts, respectively. KRAS mutations were: G12R/G12D/G12V/Q61H in 6/2/1/1 pts. Median overall survival was 6.6 months (m) in all pts, and 6.6/1.7 m in KRAS G12R/other KRAS (p = 0.31). Median progression-free survival was 5.7/6.2/1.5 m in all/ KRAS G12R/other KRAS (p = 0.16). Among 8 pts with evaluable response, 1 (12%) had partial response ( KRAS G12R) and 4 (50%) stable disease (3/4 KRAS G12R) as best response with disease control rate of 63%/80%/33% in total/ KRAS G12R/other KRAS (p = 0.29). Toxicity data are summarized in table 1. Conclusions: MEK-inh-HCQ demonstrated modest efficacy and manageable toxicities among KRAS G12R PDAC pts. Unlike G12D and G12V mutations in the KRAS gene, G12R is defective of conductive interactions for both PI3Ka and NF1. This ultimately results in a weakened signal being shunted through MAPK cascade and provides a unique opportunity where MEK inh can ablate signaling without the alternate pathways and WT-RAS isoforms compensating. Furthermore, as activation of PI3Ka is known to suppress autophagy, its lack of activation by KRAS G12R further sensitizes cells to HCQ. The combination therapy MEK-inh-HCQ is therefore mechanistically-rationale and warrants the further investigation of KRAS G12R as an actionable biomarker.[Table: see text]

Introduction Khorana score (KS) stratifies patients into low, intermediate, and high risk groups for venous thromboembolism (VTE). We examined the generalizability of the KS to risk of VTE and association with mortality. Methods A retrospective cohort study was conducted at Mount Auburn Hospital, Cambridge, Massachusetts. Patients aged 18 years or older undergoing chemotherapy were included. All patients were evaluated for a six-month period. Primary study endpoints were VTE or mortality. Results Some 277 participants were included with a mean age of 63.95 (standard deviation, SD ± 12.47). The incidence proportion was 6.13% and a total of 17 VTE events were reported over a 2.5-year period. Compared to those with a low KS (0), those with a high KS (3 or above) had 6.4 times (p=0.032) while with an intermediate KS (1-2) had 2.6 times the odds of having a VTE event (p=0.22). Those who had a VTE had 4.03 times the odds of death compared to those who did not have a VTE (p=0.006). Compared to those with a low KS, those with a high KS had 5.7 times (p=0.02) the odds of six-month mortality and 5.04 odds (p=0.001) of mortality at any time. Conclusion High KS was associated with increased odds of VTE and mortality in our study.

596 Background: Genomic alterations (GA) that drive cancer development and predict therapeutic response remain elusive in patients (pts) with KRAS WT PDAC. We interrogated our institutional database to identify actionable GAs in pts with metastatic, KRAS WT PDAC and analyzed the therapeutic impact of matched TT. Methods: We reviewed electronic medical records of KRAS WT PDAC pts (n=24) who underwent comprehensive genomic profiling (CGP) utilizing Foundation One CDx (25.0%) or Tempus (75.0%) between 2015-2021. Duration of response (DOR) was calculated from date of treatment (Tx) initiation to Tx discontinuation. Overall survival (OS) was measured from the date of the diagnosis (Dx) of advanced disease (AD) to death or last follow-up. OS was estimated using the Kaplan-Meier method, with at-risk periods left-truncated at the time of CGP. The effect of covariates on survival was evaluated using Cox proportional hazards regression. Results: Of the 24 KRAS WT pts, 14 (58%) had AD: 8 (57%) pts had metastatic disease at or shortly after Dx, 6 (43%) pts developed metachronous recurrence. Median age at Dx for pts with AD was 65, and 57% were female. Seven of 14 pts with AD (50%) had highly actionable GA (HAGA), (Table). Pts with HAGA demonstrated durable responses to TT (Table) with manageable toxicities. Pts with HAGA had a median OS of 28 mo compared to 5.9 mo for those without (Hazard Ratio = 0.47, p = 0.33). Conclusions: The sustained therapeutic benefit noted with TT matched to HAGA in pts with KRAS WT PDAC underscores the need for systematic interrogation of the somatic genome in PDAC pts. Optimal sequencing of cytotoxic therapy with TT and its impact on modulating clonal selection pressure in pts with KRAS WT PDAC merits prospective evaluation.[Table: see text]

Background: While most patients (pts) with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of pts will experience early progression, which is associated with inferior survival. Earlier identification of high-risk FL pts could allow for intervention with novel treatments to forestall early progression. Current prognostic tools are imperfect, particularly for pts receiving bendamustine-based regimens, and novel biomarkers are needed. In Hodgkin lymphoma, interim positron emission tomography (iPET) evaluated based on Deauville score (DS) is highly prognostic and is used to guide response-adapted therapy. The prognostic value of iPET using DS has not yet been assessed in a large population of FL pts receiving frontline CIT. We hypothesized that iPET would predict progression-free survival (PFS) in this population which could support PET-guided treatment approaches. Methods: We retrospectively identified pts with a diagnosis of FL (grade 1-3B) who initiated frontline CIT at Dana-Farber Cancer Institute from 1/2005-3/2019 and underwent an iPET after 2-4 cycles of CIT. Pts who received radiation (XRT) prior to CIT were included. Baseline, interim, and (when available) end-of-treatment (EOT) PET scans were reviewed by a nuclear medicine radiologist in a blinded fashion and assigned a DS of 1-5. Results: 118 pts were identified. The median age was 55 (range 26-82). 73 pts (62%) had grade 1-2 FL, 17 pts (14%) grade 3A, 15 pts (13%) grade 3B, 12 pts (10%) grade 3 NOS, and 1 pt (1%) grade not reported. FLIPI score was low for 32%, intermediate for 42% and high for 26%. In total, 5 pts (4%) received XRT before CIT. The most common CIT regimens were RCHOP (54%) and BR (42%) (Table 1). 107 pts (91%) received 6 cycles of CIT and 4 pts (3%) received 8 cycles, while 7 pts (6%) discontinued CIT after 4-5 cycles due to cytopenias (4), heart failure (1), infection (1), or pt decision (1). 88% of iPETs were performed after 3 cycles. iPET DS was 1 for 18%, 2 for 57%, 3 for 13%, 4 for 9%, and 5 for 3%. EOT PET was available for review for 112 pts (95%) and demonstrated DS of 1 for 32%, 2 for 56%, 3 for 3%, 4 for 4%, and 5 for 5%. After CIT, 29 pts (25%) received a median of 9 doses (range 1-13) of rituximab maintenance (RM) and 2 pts (2%) received consolidative XRT. With a median follow-up of 54 months (range 5-186), the 4-year (yr) PFS and overall survival (OS) for the entire cohort were 69% (95% CI 58-77%) and 94% (95% CI 87-98%), respectively. iPET was a significant predictor of PFS (p=0.0011 for 5 categories). Compared to pts with an iPET DS of 1-2, pts with a DS of 3 (HR 3.0, p=0.006) or a DS of 4-5 (HR 3.4, p=0.004) had inferior PFS (Figure 1) and were grouped together in a +iPET group (n=30) for all analyses. The 4-yr PFS for DS 1-2 and DS 3-5 pts were 77% and 46%, respectively (HR 3.2, p EOT PET was also a significant predictor of PFS (p Conclusions: Our study suggests that iPET may be a useful prognostic marker in FL. Additionally, iPET interpretation may be different in FL compared to other lymphomas. In this cohort, pts with a DS of 3 on iPET had inferior PFS with outcomes similar to those of pts with a DS of 4-5. A DS of 3-5 on iPET appears to predict earlier progression independent of EOT PET while providing response-driven prognostic information earlier in a patient's treatment course. If validated, these results suggest that iPET could be investigated as a tool for response-adapted treatment strategies in FL. Disclosures Salles: BMS/Celgene: Honoraria, Other: consultancy or advisory role; Kite, a Gilead Company: Honoraria, Other: consultancy or advisory role ; Epizyme: Honoraria, Other: consultancy or advisory role; Janssen: Honoraria, Other: consultancy or advisory role; MorphoSys: Honoraria, Other: consultancy or advisory role; Novartis: Honoraria, Other: consultancy or advisory role; Roche: Honoraria, Other: consultancy or advisory role; Abbvie: Other: consultancy or advisory role; Autolos: Other: consultancy or advisory role; Debiopharm: Consultancy, Honoraria, Other: consultancy or advisory role; Genmab: Honoraria, Other; Karyopharm: Honoraria; Takeda: Honoraria. Zelenetz:MEI Pharma: Research Funding; Celgene: Research Funding; Sandoz: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Celgene: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnology: Consultancy; MorphoSys: Research Funding; Gilead: Consultancy; Genentech/Roche: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Roche: Research Funding. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Crombie:AbbVie: Research Funding; Bayer: Research Funding. Davids:Ascentage Pharma: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; BeiGene: Consultancy; Celgene: Consultancy; Eli Lilly: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; Genentech: Consultancy, Research Funding; Janssen: Consultancy; Bristol Myers Squibb: Research Funding; Merck: Consultancy; Research to Practice: Honoraria; Syros Pharmaceuticals: Consultancy; Zentalis: Consultancy; Sunesis: Consultancy; Gilead Sciences: Consultancy; Novartis: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding. Fisher:Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees. Jacobsen:Merck: Consultancy; Acerta: Consultancy; Astra-Zeneca: Consultancy; Pharmacyclics: Research Funding; F. Hoffmann-LaRoche: Research Funding; Novartis: Research Funding; Takeda: Honoraria. LaCasce:BMS: Consultancy; Research to Practice: Speakers Bureau; UptoDate: Patents & Royalties. Armand:Sigma Tau: Research Funding; Tensha: Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; IGM: Research Funding; Adaptive: Consultancy, Research Funding; Celgene: Consultancy; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Genentech: Research Funding.

Background: While autologous stem cell transplantation (ASCT) can be curative for patients (pts) with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), relapse remains common. With the emergence of novel effective therapies, it is even more important to identify pts at high risk of treatment failure who may not benefit from ASCT, and pts with impending post-ASCT relapse who may be candidates for pre-emptive interventions. We assembled cohorts of DLBCL pts who underwent ASCT and had apheresis stem cell (ASC) samples or serially collected post-ASCT peripheral blood mononuclear cell (PBMC) and plasma samples. We hypothesized that circulating tumor DNA (ctDNA) identified using immunoglobulin-based next generation sequencing (IgNGS) in ASC or PB samples could predict relapse. Methods: Samples from 3 cohorts were analyzed. Pts in cohort 1 (C1) underwent ASCT at Dana-Farber Cancer Institute (DFCI) from 2003-2013 (Herrera, ASH 2015). Archival tumor tissue and ASC samples were retrospectively collected for analysis. Pts in cohort 2 (C2) were prospectively enrolled on a banking protocol at DFCI and underwent ASCT from 2014-2016. Pts in cohort 3 (C3) underwent ASCT from 2015-2016 and participated in a multicenter phase II trial of post-ASCT pembrolizumab maintenance (PM) (Frigault, Blood Adv 2020). Pts in C2/C3 had tumor tissue and serially collected post-ASCT PBMC and plasma samples as mandated by protocol, and a subset had available pre-ASCT PB or ASC samples. Because PM did not demonstrate a clear benefit in the trial, all cohorts were analyzed together. IgNGS (Adaptive Biotechnologies; Seattle, WA) was performed, as previously described (Armand, BJH 2013). In all cases, ctDNA testing was not performed in real-time or used to drive clinical decisions. Results: 152 pts were enrolled. Among 141 pts with sufficient DNA for testing, a clonotype was identified in 112 (78%) with a higher detection rate in more recent cohorts - C2 (93%) and C3 (90%) vs C1 (67%). Among 97 pts with an available ASC sample, 23 (24%) were ctDNA-positive (pos). With a median follow-up among survivors of 69 months (m) (range 13-185), the 5-year (y) progression-free survival (PFS) for ASC ctDNA-pos and ASC ctDNA-negative (neg) pts were 13% (95% CI 3-30%) and 52% (95% CI 40-63%), respectively (HR 2.8, p 56 pts had a median of 3 (range 1-8) post-ASCT plasma samples available for analysis. Within this cohort, 25 pts relapsed and 2 pts died in remission. 21 pts (38%) had detectable ctDNA in a median of 2 post-ASCT samples (range 1-5); among them, 18 (86%) relapsed with a median lead time from first ctDNA detection to relapse of 52 days (range 0-518). Among the 3 ctDNA-pos pts who did not relapse, 2 had detectable ctDNA at a single time point and subsequently became ctDNA-neg, and 1 developed acute myeloid leukemia and underwent allogeneic transplantation. Among 20 pts who relapsed and had ≥1 plasma sample available within 100 days of relapse, 18 (90%) had detectable ctDNA. PBMC testing had inferior performance characteristics (Table). Conclusions: Identification of ctDNA using IgNGS within an ASC sample is a powerful predictor of post-ASCT relapse and provides (at least in this cohort) a better way to predict relapse than pre-ASCT PET. Detection of ctDNA in pre-ASCT plasma also appears to be predictive of relapse. In ctDNA-pos pts, given the dismal PFS, strong consideration could be given to alternative treatment strategies, e.g. CAR-T cell therapy. Furthermore, detection of ctDNA in post-ASCT plasma samples is closely associated with impending relapse, which provides an attractive platform for pre-emptive therapeutic intervention. Figure Disclosures Brown: Dynamo Therapeutics: Consultancy; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Octapharma: Consultancy; Pfizer: Consultancy; Acerta: Consultancy; Sun: Research Funding; Genentech: Consultancy; Rigel Pharmaceuticals: Consultancy; Eli Lilly and Company: Consultancy; Juno/Celgene: Consultancy; Invectys: Membership on an entity's Board of Directors or advisory committees, Other: DSMC; Gilead: Consultancy, Research Funding; Astra-Zeneca: Consultancy; Janssen: Honoraria; Sunesis: Consultancy; Novartis: Consultancy; Loxo: Consultancy, Research Funding; Nextcea: Consultancy; MEI Pharma: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Catapult: Consultancy; BeiGene: Consultancy; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy. Crombie:AbbVie: Research Funding; Bayer: Research Funding. Davids:Gilead Sciences: Consultancy; Zentalis: Consultancy; Sunesis: Consultancy; Syros Pharmaceuticals: Consultancy; Research to Practice: Honoraria; Merck: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Eli Lilly: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy, Research Funding; BeiGene: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; AbbVie: Consultancy; Novartis: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding. Fisher:Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees. Jacobsen:Merck, Pharmacyclics, F. Hoffmann-LaRoche, Novartis: Research Funding; Takeda: Honoraria; Acerta, AstraZeneca, Merck: Consultancy. LaCasce:BMS: Consultancy; Research to Practice: Speakers Bureau; UptoDate: Patents & Royalties. Dahi:Kite: Consultancy. Nieto:Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Astra Zeneca: Other: Grant Support. Chen:Incyte Corporation: Consultancy; Takeda: Consultancy; Magenta: Consultancy; Kiadis: Consultancy; Actinium: Other: Data and Safety Monitoring Board Member; Equillium: Other: Data and Safety Monitoring Board Member; AbbVie: Other: Data and Safety Monitoring Board Member. Herrera:Pharmacyclics: Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Karyopharm: Consultancy; Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding. Armand:IGM: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Affimed: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Infinity: Consultancy; Otsuka: Research Funding; Genentech: Research Funding; Roche: Research Funding; Tensha: Research Funding; Merck: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy, Research Funding; Sigma Tau: Research Funding.

Background Although classical Hodgkin lymphoma (cHL) is highly curable, 20%-30% of patients will not be cured with conventional treatments. The programmed death-1 (PD-1) inhibitors (PD-1i) nivolumab and pembrolizumab have been Food and Drug Administration-approved for relapsed/refractory (R/R) cHL. There is limited data on the real-world experience with PD-1i in cHL and it is unknown whether fewer selected patients treated with PD-1i derive benefits similar to those observed in published trials. Materials and methods We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD-1i in the nontrial setting. The primary objective was to describe progression-free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post-PD-1i therapies. Results The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD-1i were 68%, 45%, and 23%, respectively. Twelve-month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety-six percent of patients with CR continue to respond at a median follow-up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD-1i demonstrated objective responses. Conclusion To our knowledge, this analysis is the first describing real-world experience with PD-1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD-1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post-PD-1i systemic therapies appear active. These results support the effectiveness and tolerability of PD-1i therapy in R/R cHL in a real-world setting. Implications for practice Two PD-1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real-world setting in the U.S. The present study demonstrates that patients treated in a real-world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD-1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD-1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

Background: Comprehensive Genomic Profiling (CGP) is performed routinely in patients (pts) with metastatic solid tumors (MSTs) to guide treatment. However, there is variability in the interval between metastatic diagnosis (MDx) and performance of CGP based on histology and/or provider preference. We analyzed the CGP utilization patterns and its impact on outcomes at our academic medical center. Methods: All MST pts with CGP data (January 2012 - April 2020), their date of MDx, and the date of CGP were identified by electronic medical record review. Pts who had CGP after MDx were divided into tertiles (T1-earliest, T3-latest) within each cancer type, while some pts had CGP performed prior to MDx (pre-mets). Overall survival (OS) was estimated from the time of MDx with left truncation at the CGP time. Cox regression model was used to estimate the impact of ‘timing of CGP' on survival for individual cancer (CA) types. Results: Among 1,358 pts identified, 710 (52%) were female, 1,109 (82%) Caucasian, 186 (14%) Afro-Americans, and 1,320 (97%) non-Hispanic. Lung (254; 19%), colorectal (203; 15%), gynecologic (121; 8.9%), pancreatic (106; 7.8%) and connective tissue/soft tissue CAs (95; 7%) were the most frequently identified. Sex, race, and ethnicity had no impact on the time interval between MDx and CGP with 2 exceptions - Hispanics with lung CA and females with pancreas CA had delayed CGP compared to non-Hispanics and males respectively (p =0.019, p =0.025). The median time to CGP after MDx was shortest for urothelial CA (2.4 months) and longest for prostate CA (22 months). Pts with lung [T2 Hazard ratio (HR) of 2.25, p Conclusion: Early CGP after MDx may have a greater impact on OS in CA types with more actionable therapeutic targets. The inherent bias associated with limiting the analyses only to pts who had CGP performed hampers our ability to contrast these results with those who did not have CGP performed. The establishment of national quality metrics for CGP utilization by CA type is imperative. Citation Format: Bicky Thapa, Gulrayz Ahmed, Matthew Lasowski, James P. Thomas, Honey V. Reddi, Michael T. Zimmerman, Raul Urrutia, Aniko Szabo, Ben George. Comprehensive genomic profiling - does timing matter [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2243.

e16233 Background: Chronic inflammation from AID and the resultant immunosuppression from treatment increases the risk of various malignancies. Risk of PDAC is increased in patients (pts) with AID, however, there is paucity of cancer specific outcome data in these pts. We retrospectively reviewed the outcomes of pts with PDAC and AIDs to include Crohn’s disease (CD), ulcerative colitis (UC) and rheumatoid arthritis (RA). Methods: All pts aged 18 or older, diagnosed with PDAC in the setting of CD, UC and RA between January 2010 and December 2019 were included. Patients were identified using our institutional Clinical Research Data Warehouse (CRDW) and chart review. Clinical data was obtained by querying a cohort discovery tool (i2b2) from the CRDW with IRB approval. Pts with incomplete documentation were excluded. Descriptive statistics were used to report demographics. Overall survival (OS) was calculated from the time of diagnosis of PDAC to the date of death or last follow-up. Deaths from any cause were included in the survival analysis. OS and relapse free survival (RFS) were estimated using Kaplan-Meier methods. Results: We identified 51 pts who met inclusion criteria; 26 (51%) had RA, 15 (29.4%) had UC and 10 (19.6%) had CD. Median age at diagnosis of PDAC was 55.2 years, 49% were male (Table 1). Median duration from diagnosis of AID to PDAC for pts with CD, RA and UC was 173, 107 and 105 months, respectively. Metastatic disease at diagnosis was present in 19 (37.3%) of the 51 pts and 32 (62.7%) had localized disease (LD). Among the 17 pts with LD who underwent surgery, 6 (35.3%) experienced relapse with a median RFS of 14 months. The median OS of pts with LD who underwent surgery was 44 months compared to 8.25 months for those who did not. Among the 19 pts with metastatic disease at diagnosis, 0, 1, 2 & 3 lines of chemotherapy was received by 4 (21.1%), 8 (78.9%), 3 (36.8%) and 2 (21.1%) of pts, respectively. Median OS of patients with metastatic disease at diagnosis was 8.9 months. Conclusions: The inflammatory milieu and immunosuppression associated with AID treatment may be responsible for the early onset of PDAC in these pts. Although our sample size is small, pts with AID and PDAC who complete all planned curative intent therapy appear to have excellent outcomes, emphasizing the importance of early diagnosis and perhaps routine screening in pts with AID. Receipt of chemotherapy and OS of pts with metastatic PDAC in the setting of AID does not appear to be significantly compromised despite their exclusion from several clinical trials. Demographics.[Table: see text]

4136 Background: The genomic alterations which characterize PDAC holds great promise for novel therapeutic interventions. Constitutive signaling via mutated KRAS is considered the signature pathognomonic alteration in PDAC, less than 10% of patients (pts) have tumors which are KRAS wild type (WT). We retrospectively reviewed our institutional genomic database to characterize PDAC pts with KRAS WT tumors. Methods: We reviewed electronic medical records of PDAC pts who underwent comprehensive genomic profiling (CPG) utilizing Foundation One CDx (50.6%) or TEMPUS (49.4%) between 2015-2020. Demographic and disease characteristics were compared between cohorts using Wilcoxon rank-sum test or chi-square tests. Left truncation at the time of CGP was used to account for the time of entry into the study cohort. Kaplan-Meier method was used for survival curve estimation, and log-rank test was used for between-group comparison. Cox regression was used to adjust for confounders. Results: We identified 235 patients: median age at diagnosis was 65 years and 52% were male. Clinical stages at diagnosis were localized (resectable/borderline resectable), locally advanced, or metastatic in 105 (44.7%), 61 (26.0%), and 69 (29.4%) patients, respectively. KRAS status was mutated in 212 (90%) patients: the most common alterations being G12D (48%), G12V (28%) and G12R (14%). KRAS WT status was noted in 23 (9.8%) pts, actionable genomic alterations in this subgroup are summarized in the table. Baseline demographic and treatment characteristics were similar between patients with KRAS mutated and WT tumors. Of the 23 patients with KRAS WT tumors, 16 (69.6%) completed all planned curative intent therapy compared to 121 (57.3%) of the 212 KRAS mutated pts (p=0.26). Median Overall Survival of patients with KRAS mutated tumors was 18.6 months compared to 44.1 months for WT pts (p=0.03). Adjusting for stage, WT vs. mutated status was associated with a 62% decreased hazard of death (HR 0.38 [0.18-0.83]; p=0.016). Conclusions: Patients with KRAS WT PDAC appear to have a distinct biology compared to those with KRAS mutations, meriting exploration in larger data sets. Further, comprehensive whole genome or transcriptomic characterization of KRAS WT tumors is necessary to identify putative driver alterations as well as actionable therapeutic targets.[Table: see text]

Chemotherapy-induced lung toxicity can affect pulmonary parenchyma, pleura, airways, pulmonary vascular system, mediastinum or the neuromuscular system that is responsible for respiration. Chemotherapy-induced pulmonary toxicity is a diagnosis of exclusion. When the patients with malignancies develop pulmonary toxicity such as pneumonitis and distinguishing it from alternative diseases such as infectious, thrombotic, cardiac, malignant or exacerbation of chronic lung conditions can be difficult. Moreover, such patients are often immunosuppressed, physically stressed from the underlying disease and the cancer treatment and hence, more susceptible to usual and unusual or opportunistic infections. We describe a patient with pancreatic cancer who was assumed to develop recurrent chemotherapy-induced pneumonitis to various agents, including irinotecan and docetaxel, but subsequently proved to have reactivation of tuberculosis (TB). With tuberculosis not being uncommon in cancer patients, we now believe that his symptoms could all have been because of an active tuberculosis infection, especially with his latent TB history and pulmonary symptoms. Information about the link between the treatment of solid-organ cancers and TB is very limited. Our case underlines the recognition about this link of chemotherapy and TB as well as remind us of the lack of widely accepted and established standards for both screenings for latent TB and for the treatment of active TB in the patients undergoing systemic treatment. A simple test such as a tuberculin skin test or QuantiFERON-TB Gold test can be used to rule out latent TB before beginning radiotherapy or chemotherapy in these patients. Clinicians must be cognizant of this condition to prevent further morbidity and mortality in these cancer patients and include activated TB in the differential diagnosis of pulmonary toxicity suspected in a patient undergoing chemotherapy with unexplained pulmonary findings.

Introduction: Although venous thromboembolism (VTE) is a well-known complication of cancer, predicting and mitigating the risks associated with VTE related to cancer remain a challenge.1 In 2008, Khorana et al. proposed an objective risk model that could be used to stratify patients into low, intermediate and high risk groups for VTE.2 There is also some evidence that a high KS is associated with increased mortality.3,4,5 This coding system, termed the Khorana score (KS), is based on widely available objective data and has been studied in academic teaching hospitals to assess risk of VTE. Here we examined the generalizability of the KS to risk of VTE in a community hospital setting and examined association with mortality. Methods: A retrospective cohort study was conducted at the outpatient infusion clinic at Mount Auburn Hospital (MAH), Cambridge, MA. Patients aged 18 years or older undergoing chemotherapy for a new diagnosis of cancer, or undergoing new chemotherapy for disease progression or re-occurrence with an interval of >3 months from prior chemotherapy were included. Exclusion criteria included insufficient documentation, on clinical trials, surgery Results: A total of 339 patients were screened and 277 met the eligibility criteria. The mean age of participants was 63.95 (SD ± 12.47). Detailed demographics are presented in Table 1. The incidence proportion (cumulative incidence) of VTE was 6.13%. There were no cases of VTE reported in patients with cancer stage 1 while there were increasing numbers of VTE events with increasing cancer stage (3, 4 and 10 cases were reported with stages 2, 3 and 4 respectively). Patients with metastatic cancer had a greater risk of having a VTE event than those without metastatic cancer though this was not statistically significant (OR= 2.28; 95% CI 0.84 to 6.18; p=0.11). Compared to those with a low KS (0), those with a high KS (≥3) had a significantly greater risk of a VTE (OR, 6.40; 95% CI, 1.17 to 34.58; P=0.03). We observed a modest trend for increased risk of VTE with aspirin use (OR, 2.81; 95% CI, 0.98 to 8.04; P = 0.06) though this was not statistically significant. An increased risk of death was observed among those patients who had a VTE compared to those who did not have a VTE (OR, 4.03; 95% CI 1.48 to 11.02; P = 0.006). Compared to those with a low KS, those with a high KS had a greater risk of mortality at 6 months (OR, 5.70; 95% Cl 1.32 to 24.66, P=0.02) and up to 2.5 years (OR, 5.04; 95% Cl 1.87 to 13.54, P=0.001) after adjusting for cancer stage. Compared to those with a low KS, those with an intermediate KS (1-2) also had an increased risk of mortality over the 2.5 year study period when adjusted for cancer stage (OR, 2.54; Cl 1.19 to 5.42; p = 0.012) though 6 months mortality was not statistically significant (OR, 2.54; 95% CI 1.19 to 5.42; p = 0.26). Limitations: This was a retrospective single center study over a small time period. We were limited by the small sample size which may account for the large confidence intervals and lack of precision in the odds ratio estimates. Use of aspirin was not randomized and the effect of specific chemotherapies were not evaluated. Conclusion: In community hospital setting, high KS was associated with increased odds of VTE. High and intermediate KS were also statistically associated with increased mortality over the 2.5 years study period. We did not observe a protective effect on VTE with aspirin use, instead there was a weak trend to increased risk with its use. Disclosures No relevant conflicts of interest to declare.

To determine the attitude of general practitioners towards continuing medical education (CME) and reasons motivating or hindering them from attending CME procedures, we conducted a cross-sectional survey from November 2013 to April 2014 in Karachi. Three hundred general practitioners who possessed a medical license for practice in Pakistan filled a pre-designed questionnaire consisting of questions pertaining to attitudes towards CME. Data was entered and analyzed using SPSS v16.0. 70.3% (n = 211) of the participants were males. Mean age was 47.75 ± 9.47 years. Only 67.33% knew about CME and only 52% had attended a CME session. Reasons for attending CME procedures reported were: need for updating knowledge, skills and competencies (67.30%), opportunity to meet colleagues (18.58%) and presenting scientific papers (8.97%). Mean Likert score was 1.67 (±0.667) for those who thought CME is worthwhile and 1.44 (±0.686) for those who consider their clinical duties as the major hurdle in attending CME procedures. Most common cause for not attending CME was lack of knowledge (32.66%) followed by time constraint (24%). Most physicians were not sufficiently informed about the potential benefits of CME and had never attended a CME session. Most common reason for attending CME procedures reported was need for updating knowledge, skills and competencies while reasons hindering physicians from attending CME were lack of knowledge and time constraint.

Background: There is limited data comparing the outcomes of the two most common (FM or FB) RIC regimens in AML. Previous smaller retrospective studies suggest increased non-relapse mortality (NRM) but decreased relapse with FM based RIC with a variable effect on overall survival as compared to FB. Methods: AML patients aged ≥18 years who had their 1st allo HCT using FM or FB (iv Bu only) RIC between 2001-2015 who had data reported to CIBMTR were studied. Patients with cord blood or identical twin donors, TBI as a part of conditioning, GVHD prophylaxis with T cell depletion/CD34 selection or post HCT Cyclophosphamide were excluded. Primary endpoint was overall survival (OS), and secondary endpoints included non-relapse mortality (NRM), relapse, leukemia free survival (LFS) and acute and chronic GVHD. Cox proportional hazards multivariable regression was used to compare the two RIC regimens while adjusting for significant patient, disease and transplant related factors. Major subgroup analysis included patients in CR pre-HCT. Results: 622 patients received FB and 791 had FM RIC. Median age of the FM group was 59 years, range (18 to 76) and median age of FB group was 61 years, range (18- 77). Compared to FB RIC regimen, FM group had more patients with active disease (36% vs 18%), with mismatched donors (24% vs 15%), with bone marrow grafts (19% vs 9%), HCT before 2005 (29% vs 12%) and without ATG/alemtuzumab (58 % vs 48%); but fewer patients in CR1 (46% vs 62%) and matched sibling donor grafts (21% vs 30%). There was significantly increased NRM in the FM vs FB within 3 mo post HCT (hazard ratio (HR)=3.85 (95% confidence intervals [CI] 2.46-6.03), but not beyond 3 mo FM vs FB , HR= 1.14 (95% CI 0.88-1.47). There was significantly decreased relapse for FM vs FB, (HR=0.65 (0.55-0.76), p Conclusion: The current study of this large CIBMTR AML transplant cohort has showed that in these two most common RIC regimens for allogeneic HCT, long-term survival with FM was similar to FB. While the FM regimen showed higher early NRM, it was associated with lower risks of relapse. Further analysis to evaluate FB and FM regimens in relationship to comorbidities, comprehensive geriatric assessments, and presence of minimal residual disease is warranted to better define the relative efficacy of these two RIC regimens in AML. Disclosures Weisdorf: Pharmacyclics: Consultancy; Seattle Genetics: Consultancy; SL Behring: Consultancy; FATE: Consultancy; Equillium: Consultancy.

Health insurance is the financial protection against the healthcare costs arising from disease or accidental bodily injury. Social health insurance (SHI) is a type of health insurance that provides insurance for the population of a country and covers the costs of healthcare. The SHI model is still in its early stages in Pakistan. Hospitals and healthcare are now the responsibility of the provincial governments and modified SHI models have been implemented in some provinces, while others are still contemplating on its workings. However, SHI in Pakistan cannot work unless a national level strategy is implemented.

Acute respiratory infections (ARI) are the leading cause of death among young children in developing countries. Every year, they affect an estimated 156 million children below the age of five worldwide, of which 151 million children are in the developing world. Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and south-east Asia with majority of cases occurring in India, China and Pakistan. Causative agents are Streptococcus pneumoniae for community acquired pneumonia, chlamydia and mycoplasma for ages less than 5 years, Mycoplasma pneumoniae in school-going children, Chlamydia trachomatis in infants between two weeks and four months of age and influenza virus and RSV for pre-school age.

Background Weight misperception is the discordance between an individual’s actual weight status and the perception of his/her weight. It is a common problem in the youth population as enumerated by many international studies. However data from Pakistan in this area is deficient. Methods A multi-center cross-sectional survey was carried out in undergraduate university students of Karachi between the ages of 15–24. Participants were questioned regarding their perception of being thin, normal or fat and it was compared with their Body Mass Index (BMI). Measurements of height and weight were taken for this purpose and BMI was categorized using Asian cut offs. Weight misperception was identified when the self-perceived weight (average, fat, thin) did not match the calculated BMI distribution. Chi square tests and logistic regression tests were applied to show associations of misperception and types of misperception (overestimation, underestimation) with independent variables like age, gender, type of university and faculties. P-value of

Background Thyroidectomy is a common surgical procedure, after which drains are placed routinely. This study aims to assess the benefits of placing postoperative drains, its complications and affects on postoperative stay, in thyroid lobectomy. Methodology Randomized Clinical Trial of 60 goitre patients undergoing lobectomy was conducted at Civil Hospital Karachi, during July’11-December’11. Patients were randomly assigned into drain and non drain groups. Patient demographics, labs and complications were noted. Ultrasound of neck was performed on both groups. For drain group, the amount of fluid present in the surgical bed and redivac drain was added to calculate fluid collection while in non drain group it was calculated by ultrasound of neck on first and second post-op days. Data was entered and analyzed on SPSS v16 using Independent T tests. Result The mean total drain output for 2 days in non-drain group was significantly lower 10.67 (±9.072) ml while in drain group was 30.97 (±42.812) ml (p = 0.014). The mean postoperative stay of drain group (79.2 ±15.63 hours) was significantly higher, as compared to mean postoperative stay of non drain group (50.4 ±7.32 hours). Mean Visual Analogue Score (VAS) for pain day 1 (6.2 ±0.997) and day 2 (4.17 ±0.95) in drain group were significantly higher compared to day 1 (2.6 ±1.163) and day 2 (1.3 ±0.877 ) of non drain group. From drain group, 2 patients complained of stridor, dyspnea on Day 1 which subsided by Day 2 and 1 case of voice change, with no such complains in non drain group. No patients from both groups developed seroma, wound infection or hematoma. Conclusion In uncomplicated surgeries especially for lobectomy, use of drain can be omitted.