Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

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Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma. We report our results of relapsed/refractory NLPHL patients who received high-dose chemotherapy and autogenic stem cell transplantation (HDC auto-SCT). Seventeen NLPHL patients received HDC auto-SCT (1996–2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15–58 years). At the time of relapse/progression, 13 (76 %) had NLPHL and 4 (24 %) had transformed diffuse large B cell lymphoma. The reason for HDC auto-SCT was refractory NLPHL in 12 patients and relapsed in 5 patients. Salvage chemotherapy was etoposide, methylprednisolone, cisplatinum, and Ara-C (ESHAP); eight patients also received rituximab with ESHAP. HDC was carmustine, etoposide, cytarabine, and melphalan (BEAM). Post-auto-SCT, complete remission was achieved in 14 (82 %), partial remission in 1 (6 %), and progressive disease in 2 (12 %) patients. The median follow-up is 63 months from auto-SCT (6–124 months). Of the nine patients who received only ESHAP, four had post-auto-SCT events versus no event in all eight patients who received rituximab+ESHAP. Kaplan–Meier estimates of 5-year event-free survival for the whole group is 76 %: rituximab+salvage (100 %) versus salvage alone (56 %), P=0.041. Overall survival is 94 %: 100 versus 89 %, respectively, P=not significant (NS). Even in refractory NLPHL patients, long-term disease-free survival is possible after HDC auto-SCT. Post-auto-SCT relapse or progression can still be managed with chemo/chemo+immunotherapy/ radiation. These encouraging results of rituximab in salvage setting should be explored further in a clinical trial setting for this patient population.

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Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.

first cluster there were 15 cases characterized by 1p and/or 16p . CREBBP and STAT6 were the most frequently mutated genes (67%), followed by TNFRSF14 (62%). Clinically, there was a female predominance (12/15; 80%), and inguinal presentation (10/15; 67%) with a frequent diffuse growth pattern (6/15; 40%). The second cluster comprised 14 cases without 1p or 16p CNN-LOH but 5 cases showed 1p deletion. CREBBP was the most frequently mutated gene (77%) followed by STAT6 (57%), KMT2D (50%), TNFRSF14 (43%) and EZH2 (36%) mutations. Clinically, there was a female predominance (9/14; 64%), some inguinal presentation (6/13; 46%) but diffuse growth pattern was rare (3 cases). In the third cluster there were 15 cases characterized by low number of genetic alterations. CREBBP was not mutated and CNN-LOH was not identified.Clinically, no sex predilection and rare inguinal presentation was observed. The BCL6 translocated cases were equally distributed among the three groups.Conclusions: BCL2-negative FLs are genetically and clinically a heterogeneous disease. Three different genetic profiles were identified that correlated with some clinical features. Groups 1 and 2 had in common the frequent occurrence of STAT6 and CREBBP mutations; however, they differed in the extent of 1p and 16p CNN-LOH and deletions. Group 3 showed low mutational level and different clinical features. MAP2K1 mutations were not identified in any of the cases indicating that BCL2-negative FL and pediatric-type FL are two different entities. Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of HL; the optimal management of stage I-II remains undefined. Methods: We conducted a multi-center retrospective study including patients (pts) ≥16 years (yr) with CD20+ stage I-II NLPHL diagnosed from 1995-2018. Management included observation after excision, single agent rituximab (R), chemotherapy (CT), radiation therapy (RT), and combined modality therapy (CMT=RT+systemic therapy). Primary outcomes were progression-free survival (PFS, by clinical, radiographic or pathologic progression) and overall survival (OS). Outcomes were measured with the Kaplan-Meier method with uni-and multivariable analyses (MVA) conducted with Cox regression. Results: We identified 437 pts with stage I-II NLPHL with median age 38 yr (range, 16-90) and median follow up of 5 yr (interquartile range=2.0-8.2). The majority were male (n=307 [70%]), had stage I (n=241 [55%]), ECOG 0-1 (n=366 [84%]), and were staged by PET-CT (n=295 [68%]). The 5-yr PFS and OS were 86.7% and 97.6%, respectively. 5-yr PFS by treatment were: 89.7% for RT (n=199 [46%], median dose 36 Gy), 92.5% for CMT (n=160 [37%]), 69.9% for CT ABSTRACT 145 (n=37 [8%]), 92.9% for observation (n=29 [7%]), and 33.3% for R (n=12 [3%]). CT only regimens were ABVD (n=27, 3 with R), R-CHOP (n=9), and R-COMP (n=1). CMT systemic therapies were ABVD (n=116, 19 with R), R-CHOP (n=24), R (n=15), MOPP (n=3), BEACOPPesc (n=1), and CVP (n=1). On univariable analysis, stage II (p=0.008), age (continuous...

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9-153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients received treatment; the response rate was 45%; complete remission in 41 (30%) and partial remission in 21 (15%) patients. 1st interventions post auto-SCT were chemotherapy (39%), radiation therapy (35%) or best supportive care (24%). Twenty-seven patients with 2nd-SCT (allogeneic (15), auto-SCT (2)) and/or brentuximab (18 patients) had superior OS (50.6 months) vs other treatments (22.5 months, P value 0.037). COX regression multivariate analysis identified post auto-SCT treatment failure before 12 months (hazard ratio (HR) 3.37, CI 1.7-6.6, P value < 0.001), presence of B symptoms (HR 2.55, CI 1.4-4.6, P value 0.002), stages III-IV (HR 2.7, CI 1.5-4.9, P value 0.001), albumin < 4 g/dl (HR 1.76, CI 1.1-2.9, P value 0.027) and tumor > 5 cm (HR 1.1.9, CI 1.13-3.25, P value 0.015) as significant risk factors; P value < 0.001. KM OS with 0-1 factor (148.6 months): 2 factors (23.6 months) and 3-5 factors (9.4 months) (P value < 0.001). OS was 63%:25%:7% respectively with 0-1:2:3-5 factors respectively (P value < 0.001). Despite high-risk factors, 2nd-SCT/brentuximab use post HDC auto-SCT failure may result in durable survival.

ABSTRACT… Introduction: National Health Information Exchange (NHIX) Systems are rapidly evolving. Due to the cyber infrastructure and improvements in communication technology, it is possible to share healthcare related data within a geographic region electronically among healthcare related autonomous entities such as physicians, hospitals, test laboratories, insurers, emerging Health Information Organizations (HIO), and even government departments. Study Design: Whether data are collected with the RCT, Quasi-experimentation or Triangulation etc., we present to explore a NHIX system for EHR that has also been implemented as a test case. We particularly propose to demonstrate a concept application, Medical Drop Box (MDB) with the key technological components of a future NHIX System for medical industry. Setting: Data from different medical settings have been used for testing the new system but the technological development has been done at IIU, Islamabad. Period: The proposed system is not time bond in terms of data collection. Basically the proposed system can handle data collected in any chunk of time in the history and can provide information as and when needed in future. Material & Methods: With MDB, a person is able to collect his/her health data and share it with the whole medical industry according to his/her own preferences and setting. Besides the technology for handing numerous forms of health care data, the main challenge of NHIX system is to allow individuals and associated medical entities to manage and share their medical information based on personal control and preferences given to each by medical laws, information rights and privacy rules. The main focus in this research paper is to make a standard medical application for the medical data that is in exchangeable format according to the standards defined in HL7. Results: The new system is able to make standardized Clinical document for medical data in exchangeable format according to HL7 standard. The MDB is the first step to setup NHIX system. With the help of MDB "Statistical Analyzer" now the health industry of the country can perform a variety of analysis for the future improvements in different health settings. Conclusions: The availability of medical data of patients on MDB cloud has improved Clinical Impact, created new Business & Services opportunities and reduced the overall Treatment Cost. Keywords:Medical Drop Box (MDB), Randomized Controlled Trial (RCT), Health Information Organization (HIO), Health Law 7 (HL7), Clinical Impact, National Health Information Exchange (NHIX).