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Background: Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for hematological disease however can be complicated by relapse or graft failure (GF), for which second-HCT and donor lymphocyte infusions (DLI) are performed. This study aimed to compare outcomes following the two interventions. Methods: We retrospectively investigated 89 patients with relapse or GF after first-HCT, 50 (56%) underwent second HCT and 39 (44%) received (DLI), from June 2011 to September 2020. Results: Median age at intervention was 55 years (19-72). Second-HCT was performed for relapse in 19 patients and for GF in 31 patients (primary GF in 11 and secondary in 20 patients), same donor was used in 25 (50%) patients. DLI was performed for relapse in 20 and for secondary GF in 19 patients. Median number of DLI administered was 2 (range 1-11). Univariate analysis demonstrated 2-year overall survival (OS) for second-HCT was superior when performed for relapse (65%) compared to GF (44%) (p=0.03). For DLI patients, 2-year OS was 49% for GF and 45% for relapse patients (p=0.49). For relapse as an indication, second-HCT demonstrated borderline superiority compared to DLI (p=0.07). Multivariable analysis demonstrated for OS for the entire cohort demonstrated donor mismatch (HR 0.50, 95%CI 0.26-0.94%, p=0.03), KPS at time of intervention (HR 2.10, 95%CI 1.14-3.85%, p=0.02) and time from first-HCT to intervention (HR 0.51, 95%CI 0.28-0.93%, p=0.03) as significant variables. Conclusion: Second-HCT may improve outcomes when performed for relapse post-transplant if patients achieve remission again, while DLI may be reserved for patients with active disease.

Background and purpose: Patients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease post salvage treatment are considered to have dismal outcome, even post autologous hematopoietic stem cell transplantation, due to disease recurrence. To minimize post-transplant relapse risk, involved field radiotherapy either to sites of bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of involved field radiotherapy in the early post- transplant period. Materials and methods We retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or had a persistent localized residual mass post-salvage treatment and consolidated with involved field irradiation within 4 months after autografting. Results No significant toxicity was noticed during the early post-radiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients are alive, 19 of whom are event-free, while 2 patients succumbed to disease recurrence and 1 to treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free and event-free survival rates were 86%, 86% and 82%, respectively. Conclusions Taking into consideration the poor-risk features of the study cohort, early post autologous hematopoietic stem cell transplantation involved field radiotherapy showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control as reflected in the promising survival rates.

Background Allogeneic hematopoietic cell transplantation (HCT) outcomes may be predicted by published risk scores; however, the ideal system has not been identified for acute leukemias. Patients and Methods We retrospectively examined the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), modified European Group for Blood and Marrow Transplantation (mEBMT), EBMT-Alternating Decision Tree (ADT), and others on 231 patients with acute leukemia. Results Acute myeloid leukemia was diagnosed in 200 patients, and acute lymphocytic leukemia was diagnosed in 31 patients. For HCT-CI, patients were grouped as 0 to 1, 2 to 3, and > 3. For mEBMT, patients were grouped as 0 to 2, 3, and > 3. For EBMT-ADT, the 100-day mortality was calculated and grouped as ≤ 4.1%, 4.1% to 11.5%, and > 11.5%. Higher HCI-CI demonstrated inferior overall survival (P = .04; c-statistic, 0.57), whereas mEBMT and EBMT-ADT did not stratify well. A new weighted score was developed that assigned 1 point for age ≥ 60 years, acute lymphocytic leukemia diagnosis, mismatch unrelated or haploidentical donor, cardiovascular comorbidity, and pre-transplant diabetes, whereas arrhythmia received 2 points. The new weighted score assigned 0 points to 88 (38%), 1 to 2 points to 121 (52%) and ≥ 3 points to 22 (10%) patients, and demonstrated improved prognostic capability compared with the other scores (P = .0001; c-statistic, 0.61). Conclusions The HCT-CI stratifies patients with leukemia for overall survival but is inferior to our single-center score, which is influenced by cardiac comorbidity and arrhythmia. Differences in pre-transplant risk scores may be related to different transplant practices.

The programmed cell death protein-1 (PD-1) inhibitor nivolumab has been recently approved as an effective and safe treatment for patients with refractory/relapsed Hodgkin’s lymphomas. Dermatological adverse events, mainly skin rash, have been reported in 1–5% of patients. We describe a case of de novo psoriasis vulgaris (PsV), diagnosed after nivolumab treatment for refractory Hodgkin’s lymphoma. After administration of 6 cycles, skin lesions appeared in the right tibia, forearms, and dorsum of hands, and biopsy confirmed the diagnosis of PsV. The lesions completely resolved after autologous stem cell transplantation (ASCT) which was performed in the context of the treatment for the primary disease. PsV is an inflammatory skin disease, and it is considered to be mediated through cytotoxic T-cells. PD-1 blockage may lead to expansion of such T-cells, resulting thus in PsV appearance. The early published studies showed that nivolumab represents a safe treatment approach. PsV occurrence has not been reported so far in patients treated with nivolumab for hematological diseases, and it seems that long-term follow-up is necessary to fully clarify the entirety of PD-1 inhibitors’ skin adverse events. Additionally, this clinical observation provides an evidence for a potential exploitation of ASCT in refractory and severe forms of PsV.

Background: Recent advances and improvement of supportive care allowed allogeneic stem cell transplantation (HCT) to be offered to selected older patients. However, data regarding outcome and factors affecting the outcomes are limited. Method: We retrospective analyzed the outcome in 332 patients, median age 65 years (60-76), who underwent HLA-matched related (n=85), matched unrelated (n=205) and haploidentical donor (n=42) HCT, between January 2014 to December 2019. Of these 60% were male. Diagnosis was leukemia: 193, MDS: 76, MF: 46 and others: 17. Graft source was PBSC in 98%. Reduce-intensity conditioning regimen was used in 95%, and in vivo T-cell depleted in 89% of patients. We categorized them to 3 age-groups (G): G1 60-65y, (n=175), G2 >65-70y (n=127), and G3 >70y (n=30).Cox models were used to compare the rates of overall survival (OS), non-relapse mortality( NRM), event free-survival (EFS), length of hospitalization for HCT, GVHD and reasons of re-hospitalization during the first year post HCT. Results: The median follow up was 14 months (range: 1-123 months). Median days of hospitalization during HCT period were 30-days (range: 20-132 days), with trend towards significance when stratified by age group (p=0.049). HCT-CI scores were 0-1 (n=143), 2-3 (n=107) and >3 (n=70). The cumulative incidences of grade II-IV acute-GVHD was 38.3% and 16.3% for grades III-IV. Moderate-severe chronic-GVHD was 23.7%. Increasing age was not associated with increases in acute GVHD (p=0.86) or chronic-GVHD (p= 0.6). Overall, 188 (56%) patients were re-hospitalized within the first 6-month of HCT, and 61 (18%) in the second 6-month period. The 2-year OS rate (Fig 1) were 56% in G1, 53% in G2 and 34% in G3 (p=0.05). The 2-year EFS rate (Fig 2) were 54% for G1, 49% for G2, and 31% for G3 (P=0.04). Cumulative incidence of NRM at 2-year (Fig 3) were 25% in G1, 36% in G2 and 52% in G3 (p=0.008). Further results are illustrated in Table 1. Risk factors such as age, KPS, HCT-CI, donor-type, readmission and GVHD were analyzed for their associations with outcomes using univariate analyses, those with significant results entered in multivariate-analysis Table 2. Patients aged 60-≤65 had significantly better EFS (p=0.04) and associated with a border line significant trend for lower NRM (p=0.05) than those aged >70. Re-admission in the first 6-month post HCT had a significant impact on the OS, EFS and NRM. HCT-CI >3 had significant impact on NRM. Conclusion: Age had a significant impact on hospitalization period during HCT. Age >70 had significant impact on EFS and trend toward higher NRM. HCT-CI, acute and chronic-GVHD and readmission in first 6-month post-HCT were significant risk factors. Readmission in the first 6 months correlated with lower OS, EFS and higher NRM. Acute GVHD III-IV or moderate-severe chronic GVHD associated with poor outcomes. Selecting patients based on HCT-CI, and good management of GVHD and post-HCT complication may improve the clinical outcome. Figure 1 Figure 1. Disclosures Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Kim: Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria; Paladin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding.

INTRODUCTION Frailty in patients undergoing hematopoietic cell transplantation (HCT) has a negative impact on survival. The inclusion of frailty evaluations before HCT is highly recommended; however, there is no consensus about the best methodology to evaluate this syndrome. In 2018 our center started a Frailty and Functionality program that involves regularly collecting information on the following eight indices in patients referred for allogeneic HCT (Salas et al., 2021): Clinical Frailty Scale (CFS), Instrumental Activities of Daily Living (IADL) test, Timed up and Go Test (TUGT), Grip Strength (GS), Self-Health Rated questionnaire (SHR-Q), Fall test, albumin (Alb), and C - reactive protein (CRP). With the recorded measurements of the eight indices and the corresponding validating process, we propose a HCT Frailty Scale. This scale is specifically designed to identify fit, pre-frail, and frail candidates for alloHCT, from better to worst probability of post-transplant survival. METHODS Between June 2018 and December 2020, 338 adults underwent alloHCT at our Institution. Frailty syndrome was evaluated prospectively in all patients at first consultation, using existing resources, after informed consent. It included measurement of the eight indices. The median time to evaluate was 5-6 minutes. Each index was given a value of 0 if normal or 1 (abnormal). Complete data were available for 298 patients that were finally included in the analysis. With this data the HCT Frailty Scale was elaborated as follows. The study cohort was split in two groups, a training cohort with 2/3 (N=200) of the patients, and a validation cohort of 1/3 (N=98), proportional to death outcomes. With the data from the training group we estimated a multivariable Cox model with overall survival (OS) as dependent variable, and the eight referenced indices as explanatory variables. Any normal result was scored 0, and based on the estimated HR coefficient from the Cox model, a proportional weight score was given to each respective index variable in the calculation of the composite HCT Frailty Scale score. The HCT Frailty index was calculated using the following formula: 1.5 *CFS, +1*IADL, +1*GS, + 1.5*TUGT, + 1*SHR-Q, +1*Falls-Test, + 1.5 *Alb, + 2*CRP. As a result, the HCT Frailty Scale goes from 0 to 10.5. The values of the scale were grouped to determine the following three groups of patients: (a) Fit patent: scale score ≤1; (b) Pre-Frail patient: 1< scale score < 5.5; (c) Frail patient: scale score 5.5 (Figure 1). RESULTS Baseline characteristics of the training and validation cohort are shown in Figure 1. Of the 200 patients included in the training cohort, the median age was 58 years (range 19-76 years); 29 (15.85%) had a KPS between 70-80%; and 56 (30.11%) a HCT-CI >3. The elaborated HCT Frailty Scale classified the 200 patients as: (a) 70 (35%) fit patients with an estimated 1-y OS of 83.7%; (b) 97 (48.5%) pre-frail patients with a predicted 1-y OS of 75.6%; and (c) 33 (16.5%) frail patients with an estimated 1-y OS of 52.8%. Of the 33 frail patients, 54.8% had a KPS between 90-100% and 48.5% had an HCT-CI CONCLUSION The HCT Frailty Evaluation Scale has been specifically designed to be applied in routine clinical practice and to patients across all ages. The scale ranges from 0 to 10.5 and the score value is calculated as the weighted sum of values of eight indexes evaluated at first consultation. The proposed scale should be of utility to identify frail and pre-frail patients that may benefit from appropriate counselling pre-transplant and individualized interventions to reverse frailty syndrome prior to alloHCT. Figure 1 Figure 1. Disclosures Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Kim: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Paladin: Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria, Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company.

For patients with Hodgkin Lymphoma (HL) who experience relapse post allogeneic stem cell transplantation, limited treatment options exist, and the ultimate outcome is poor. Recently, the programmed cell death protein-1 (PD-1) inhibitors have shown remarkable efficacy in patients with refractory/relapsed HL, also demonstrating an acceptable safety profile. However, due to effects on T-cell activity, the use of PD-1 inhibitors post allografting may potentially increase the risk of treatment-emergent graft versus host disease. We herein report the clinical course of a patient who experienced multiple relapses of HL post allogeneic stem cell transplantation. He failed several treatment modalities but he responded to escalating doses of the PD-1 inhibitor nivolumab, given at two different treatment time points, also demonstrating minimal and easily manageable toxicity.

Background The ideal conditioning regimen still remains a challenge in the autologous stem cell transplantation (ASCT) setting for relapsed/refractory Hodgkin Lymphoma (RR-HL). BEAM is the most popular preparative regimen but single agent high dose Melphalan (HDM) has also been used. However, the experience and data comparing BEAM vs. HDM are limited. Methods After the Institutional Review Board approval, we retrospectively evaluated the clinical course of 112 RR-HL patients, autografted from November 2008 till May 2017 in two different institutions. Twenty eight conditioned with HDM and compared in a matched paired analysis (1:3) with a cohort of 84 patients who received BEAM. The study groups had similar median age (30ys) and sex (M:F 1.7:1 vs. 1.8:1) and were matched for disease status before salvage (late relapse: 36 vs. 12, early relapse/primary refractory: 48 vs. 16 and disease status pre ASCT [complete remission (CR): 39 vs. 13 and partial remission (PR): 45 vs. 15]. BEAM regimen was given in the standard doses over 6 days, while HDM (200mg/m2) was given in a single day infusion. All patients received prophylaxis against microbial, fungal and viral infections; GCSF was routinely administered at the dose of 5mcg/kg at +1 day (BEAM group) and at +5 day (HDM group). The T-test and Kaplan-Meier method were used for the statistical analyses. Results The engraftment was successful; the median day for neutrophils >1000/mm3 was +11 for both groups while for platelets >20000/mm3 a faster recovery was noticed for HDM group: +13 vs. +22 days (p The 100 days non relapse mortality was acceptable for both groups: 2/84 (2.3%) in the BEAM group vs. 1/28 (3.5%) in the HDM group. Conclusion In this study, though retrospective, demonstrated that for RR-HL patients, the conditioning regimen consisting of HDM, offered at least comparable efficacy to the BEAM regimen. The earlier platelets recovery, and the shorter duration of chemotherapy administration (6 days for BEAM vs. 1 day for HDM), resulted in less hospitalization days, which along with the shorter period of GCSF administration post ASCT, may contribute to a better cost effectiveness for the HDM regimen. Nevertheless, prospective studies with larger series of patients and longer follow-up, including also a meticulous cost analysis, are warranted to determine the accurate role of single agent HDM as preparative regimen for ASCT in HL patients.

Introduction Patients with Hodgkin (HL) or Non-Hodgkin Lymphoma (NHL) who have either bulky masses at relapse or residual disease post salvage therapy, have poor outcome even after autologous stem cell transplantation (ASCT). Involved field radiotherapy (IFRT) to the bulky/residual disease sites is widely used to minimize the risk of relapse post ASCT. However, the proper time for IFRT remains controversial. IFRT delivery before ASCT could cause toxicity which might delays the ASCT increasing the risk of disease progression. Moreover, the pre-ASCT IFRT may also damages the marrow niche impairing thus the engraftment. On the contrary, the IFRT early after ASCT as adjuvant therapy (adj-IFRT) offers the advantage of irradiation delivery after sufficient disease response, without affecting the engraftment, maximizing potentially a favorable outcome, with lower irradiation in restricted areas. Aim In this study we sought to investigate the safety and the efficacy of the adj-IFRT in autografted patients for relapsed/refractory HL or NHL. Methods We evaluated retrospectively 23 patients (HL=12, NHL=11), aged of 34(16-76) years, who underwent ASCT, for primary refractory (n=15) or relapsed (n=8) disease, and received adj-IFRT post ASCT. They had previously salvaged with a median of 2 lines of therapy. Patients with bulky mass at relapse or localized residual disease post salvage treatment, were candidates for adj-IFRT. Results All patients had chemosensitive disease before ASCT. However, 15(80%) had residual disease while 4(20%) were in complete remission. The preparative regimens were: single agent Melphalan (n=9), Busulfan-Etoposide-Melphalan (n=7), BEAM (n=4) and Bendamustin-Etoposide-Cytarabine-Melphalan (n=3). Filgrastim was given at 5mcg/kg after the 5th day of graft infusion till neutrophills recovery, while anti–bacterial, -fungal, -viral and –PCP prophylaxis were administered from the conditioning regimen initiation till the completion of adj-IFRT. The engraftment was successful. No patient had any toxicity or active infection before adj-IFTR. Though we planned to give adj-IFRT within 3 months post ASCT, finally it was delivered after a median of 4,5 (2-7) months; the median irradiation dose was 30 (24-36) Gy The adj-IFRT was well tolerated. No patient experienced toxicity grade>3 and none required hospitalization. Currently, 19/23 patients are alive and well; the 5-ys overall and progression free survival rates are 70% and 64% respectively. Four patients died; 2 due to relapsed disease and 2 heavily pretreated patients due to secondary myelodyspalstic syndrome. Conclusion In this study, the use of adj-IFRT post ASCT was well tolerated and safe. The promising survival rates in these poor risk patients suggest that the adj-IFRT is also an effective approach. Well designed clinical trials are needed to clarify the role of adj-IFRT in the ASCT setting.

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for high risk hematological diseases and sustained engraftment of the donor stem cells is essential for transplant success. Graft failure (GF) is a rare, but serious complication post allo-HCT. In the presented study we aimed to assess the incidence, risk factors in a single-center population and as well the impact on transplant outcome. Methods: Between 01 January 2015 and 31 December 2018, 557 patients underwent allo-HCT at our center. Data was collected retrospectively and updated in June 2019. Cases were included regardless of the underlying diagnosis, disease status prior to transplant, preparative regimen, or stem cell source. Primary graft failure was defined as failure to achieve an absolute neutrophil count (ANC) of >500/ µL by 28 days after bone marrow (BM) or peripheral blood stem cell (PB) transplantation. In contrast, secondary graft failure was defined as cytopenias after initial engraftment (ANC 5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced. Outcomes examined included overall survival (OS), cumulative incidence of GF, non-relapse mortality (NRM) and cause of death. Results: Baseline characteristics are summarized in (Table 1). GF was seen in 43 (7.7%) patients. Of these 43 patients, 9 (21%) had primary GF, and 34 (79%) had secondary GF. The cumulative incidence of GF overall (primary and secondary) is 1.6% (0.8- 3.0%) at day 100 and 6.5% (4.5-8.8%) at day 800. The median survival of patients following primary GF was 41 days versus 144 days in secondary GF. At one hundred days OS in primary GF was 22% and in secondary GF was 64%. The 1y and 2y OS for secondary GF was 33% and 28% respectively (Figure 1-A). Multivariable analysis demonstrated that the (a) diagnosis/transplant indication (MDS, myelofibrosis, lymphoma or non-malignant diseases) and (b) donor type (HLA-mismatched unrelated or haploidentical) were the only factors significantly associated with increased GF (Table 2). We determined the effect of more than one of these risk factors on the occurrence of graft failure as seen in (Figure 1-B). In the absence of any of the risk factors, the incidence of GF was 3.6%. If one risk factor was present, the incidence of GF was 9.9%, and if 2 risk factors were present, the incidence of GF was 24.5%. In primary GF, 5 patients underwent second allo-HCT. In secondary GF, 15 patients (44%) underwent a second allo-HCT and another 8 patients received donor lymphocyte infusion. All the patients with primary GF died because of graft failure and its associated complications. In secondary GF, 22 patients (51%) died, 30% of causes related to infections. Conclusions: Our study showed an increased risk for graft failure following the use of mismatched unrelated or haploidentical donors for diseases such as lymphoma, myelofibrosis, myelodysplastic syndrome and non-malignant diseases. As well, we found that a presence of two risk factors puts patients at clinically significant increased risk of graft failure. More intense conditioning therapy should be considered for patients with one but in particular two risk factors. Disclosures Michelis: CSL Behring: Other: Financial Support.

Background Disease chemosensitivity to salvage treatment is a major predictive factor for a favorable outcome after autologous stem cell transplantation (ASCT) for patients with refractory lymphomas. Therefore the importance of effective and safe salvage regimens is indisputable. Methods We retrospectively compared the outcomes in terms of safety and efficacy, in 67 (HL:36, NHL:31) patients, with a median age of 34,5 (16-75)ys, who received as 1st salvage either DICEP [Dose Intensified Cyclophoshamide (1750 mg/m2), Etoposide (350 mg/m2), Cisplatin (35 mg/m2), days 1-3, (n=23)] or the widely used regimen ESHAP (n=44). Rituximab was additionally given to all CD-20 positive lymphoma patients. The statistical analyses based on the student's T-test, Kaplan Meir method and log rank test. Results In a total, 34 patients were evaluated with primary induction failure (PIF), 14 with early relapsed ( The overall response (>50% tumor reduction) rate was significantly superior for the DICEP regimen, reaching 83% (19/23 patients) vs. 60% (26/44 patients) for ESHAP group (p=0,04). Eleven out of 23 patients (48%) from the DICEP group and 14/44 (30%) from the ESHAP group achieved complete metabolic remission according to PET/CT criteria. The median hospitalization period was 20(5-25) days for the DICEP compared to 10(10-19) days for the ESHAP group. However, for the ESHAP group, an additional median of 21 (6-28) hospitalization days were required, since 12/18 non-responders patients admitted for a 2nd salvage treatment before ASCT. All but two patients (due to refractory disease) underwent ASCT. The 2-ys overall survival from disease diagnosis and the 2-ys progression free survival from 1st salvage treatment were similar for the two groups (95% vs. 88% and 70% vs. 78% for DICEP and ESHAP groups respectively). Two heavily pretreated patients from the ESHAP group developed secondary myelodysplastic syndrome post ASCT. Conclusion In our study both regimens demonstrated a safe profile. The extremely high response rates for DICEP regimen, finally resulted in less exposure to chemotherapeutic agents before proceeding to ASCT, that might led in less early and long term severe toxicity. Nevertheless, only prospective trials with large series of patients can clarify the role of DICE in the salvage treatment setting.

Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL for which optimal treatment is controversial. We retrospectively reviewed the files of patients with NLPHL diagnosed and followed up at our institution and describe clinical characteristics and outcome and explore prognostic factors for progression-free survival (PFS) and overall survival (OS). Methods We included consecutive patients diagnosed with NLPHL and followed at King Fahad Specialist Hospital, Damamm (KFSH-D), a referral center for the Eastern Province of Saudi Arabia. Primary aim of this study was to determine clinical outcomes (PFS and OS) according to treatment strategy, i.e. radiotherapy (+/- Rituximab) (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), Rituximab monotherapy (R), and active surveillance (AS). Secondary aim was an exploratory analysis of candidate prognostic factors for PFS and OS. PFS was defined as time (months) from date of diagnosis to disease progression or death from any cause. Event time distributions were estimated using the method of Kaplan-Meier and groups were compared using the log-rank test. We used univariable and multivariable PFS analyses for candidate prognostic factors. Results From 1/2006 to 12/2017 data on 49 patients treated at KFSH-D, aged 16 years (y) or older, with a diagnosis of NLPHL and with sufficient treatment and follow-up (F/U) were analyzed. Median age at diagnosis was 29y (range, 16-56), 76% were male. Histology was typical in 86% (n=42), variant in 8% (n=4), and with transformed histology at diagnosis in 6% (n=3) of cases. Disease characteristics: 63% (n=31) of patients were stage I/II and 37% (n=18) stage III/IV, B-symptoms 12%, extranodal disease 10%, splenic involvement 8%, bulky disease (≥5 cm) 12%, and bone marrow involvement 4% of patients. The German Hodgkin Study Group (GHSG) score was intermediate-risk and high-risk in 53% (n=26) and 24% (n=12) of patients, respectively. Management strategy (MS), depending on physician's preference, was RT (16%, n=8), CT (43%, n=21), CMT (27%, n=13), R (6%, n=3), and AS (8%, n=4). For patients induced with chemotherapy +/- RT, ABVD-like (+/- Rituximab) (n=25) or CHOP (+/- Rituximab) (n=9) were used in all cases. The overall response rate (ORR) for 45 patients who received treatment was 91% (complete responses (CR), 69%), 98% ORR when cases with transformed histology at diagnosis were excluded. Median F/U was 36 months (m), (range, 8-127). Overall, outcome was excellent, with 3- and 5-y PFS estimates of 80% and 75%, respectively (Figure). Overall survival was 100% with no deaths observed (Figure). The current PFS is 98%. Transformation at relapse/progression was observed in 2 patients at 36m and 45m, respectively, and remain disease free at 24m and 35m, respectively, following salvage treatment and auto-SCT. The 5-y cumulative risk of transformation (excluding cases with transformed histology at diagnosis) was 6%. Two secondary cancers were observed. Exploratory univariate analysis revealed high-risk GHLG score (P=0.001), bulky disease (P=0.001), splenic involvement (P=0.01), transformed histology at diagnosis (P=0.02), and non-RT MS (P=0.001) as risk factors for shorter PFS. In the final multivariate model, the GHLG score (P=0.01) and non-RT MS (P=0.004) were the only a risk factor for shorter PFS. In pairwise comparison, excluding patients with transformed histology at diagnosis and patients on AS, for patients with stage I/II disease, RT-based therapy was associated with improved 5-y PFS rates compared to CT-based therapy, (P = 0.02). For patients with stage III/IV disease 5-year PFS rates did not differ between RT-based and CT-based therapy (P= 0.4). For patients treated with CT, ABVD +/- Rituximab (n=13) vs CHOP +/- Rituximab (n=8) induction produced similar PFS rates at 5-years (P=0.9). Conclusion In this single center retrospective study, NLPHL had an excellent outcome. MS had an impact on PFS but not OS. High-risk GHLG score and omission of upfront RT were adversely prognostic factors for PFS. Large prospective trials are warranted to determine the optimal treatment approach for this rare B-cell lymphoma. Figure. Figure. Disclosures No relevant conflicts of interest to declare.