Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant.

Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcomes of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors in patients with ref-HL at the time of primary treatment failure and subsequent survival at the time of failure post-HDC auto-SCT. This retrospective single-institution cohort analysis using an HDC and auto-SCT database was approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used the Fine and Gray competing risk analysis method, a regression model for outcome analysis, and the Kaplan-Meier (KM) method for survival analysis. The study cohort comprised 200 consecutive ref-HL patients who underwent HDC auto-SCT between 1996 and 2019. The median patient age was 22.75 years, and median follow-up was 106 months. Post-auto-SCT disease status was complete remission (CR) in 122 patients (61%), partial remission in 22 (11%), and progressive disease in 47 (23.5%). KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5 years, 49.3%; 10 years, 45.5%). Median overall survival (OS) was 168.6 months (5 years, 61.2%: 10 years, 56.2%). Eighty-five patients (44.5%) died, 69 (34.5%) due to disease. Multivariate analysis identified similar adverse factors for both PFS and OS. For PFS, these adverse factors included stage III-IV at relapse (hazard ratio [HR], 1.65; P = .045), mediastinal involvement (HR, 2.01; P = .009), and absence of CR after salvage chemotherapy (HR, 2.2; P = .001). PFS with 0 or 1 adverse factors (not reached), 2 adverse factors (40.8 months), and 3 adverse factors (5.4 months) was significant (P < .001). For OS, significant adverse factors included stage III-IV at relapse (HR, 1.68; P = .045), mediastinal involvement (HR, 2.52; P = .007), and no CR after salvage chemotherapy (HR, 2.15; P = .004) were significant. OS with 0 or 1 adverse factors (not reached), 2 adverse factors (148.5 months), and 3 adverse factors (34.4 months) was significant (P < .001). The median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4 months) (P < .001). OS with 5 risk factors present at HDC auto-SCT failure- stage III-IV, failure at <12 months, tumor >5 cm, B symptoms, and low serum albumin-was 152 months for 0 or 1 risk factors, 30.9 months with 2 risk factors, and 9.45 months with 3 to 5 risk factors (P < .001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.

Comparison of 18F-labelled fluoro-2-deoxyglucose-PET with conventional computed tomography for staging and response assessment in paediatric and adult patients with nodular lymphocyte-predominant Hodgkin's lymphoma.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding 18F-labelled fluoro-2-deoxyglucose (FDG)-PET use in NLPHL. We are reporting our experience with FDG-PET utility in staging and response assessment NLPHL patients. METHODS: We retrospectively studied a population of all newly diagnosed or relapsed/refractory patients who underwent both pre-treatment contrast-enhanced computed tomography (CeCT) and an FDG-PET and also at the end of planned treatment. RESULTS: We identified 68 patients found to have in total 312 scans, 78 paired pre-therapeutic and post-treatment CeCT and FDG-PET scans. Among them, 55 were male, with a median follow-up was 48 months. Median SUV-max was 8.3 (2.0-21.0). FDG-PET and CeCT were concordant in 80% (62/78) of staging scans. In 20% (16/78) of patients in whom a discordance was observed, FDG-PET resulted in upstaging in 13 scans and downstaging in 3 scans. The sensitivity of CeCT was 92% for nodal staging and 42% for extralymphatic staging when compared to FDG-PET. The specificity of CeCT was 98% as compared to FDG-PET. For response assessment, there was poor agreement between the CeCT and FDG-PET in assigning complete remission of disease scores as FDG-PET was able to identify the absence of disease despite the presence of a radiologically evident residual mass on CeCT. The sensitivity for CeCT compared to FDG-PET was 100% while the specificity was 43% for detection of post-treatment response. CONCLUSION: For NLPHL, pre-therapeutic FDG-PET scan is better than CeCT staging. FDG-PET has much better specificity for response assessment than CeCT.

Nodular lymphocyte-predominant Hodgkin lymphoma characteristics, management of primary and relapsed/refractory disease and outcome analysis: the first comprehensive report from the Middle East.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of Hodgkin lymphoma. There is limited data on treatment, management of refractory and relapsed disease, and long-term outcome. Many registries or country-wide data reports are unable to provide detailed primary and subsequent management. We are reporting our observation on patient's characteristics, management, and outcome. METHODS: This single-institution retrospective cohort analysis includes NLPHL patients seen from 1998 to July 2019. We used Fisher's exact test, chi-square, and Kaplan-Meier (KM) method for various analyses. RESULTS: Two hundred patients were identified, (6.34% of all the HL). Male:female was 3:1. The median age at diagnosis was 22 years (4-79 years). Stage I-II in 145 (72.5%) cases. One hundred patients (50%) received chemotherapy, 68 (34%) chemotherapy + radiation therapy (RT); 87% of all chemotherapy was ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Thirteen patients (6.5%) received RT alone and 16 (8%) had surgery alone. Complete response in 82%, partial response in 5.5% and progressive disease in 10.5%. The median follow is 60 months (5-246). Median 5 and 10 years overall survival (OS) is 94.8 and 92.4% (stages I-II, 97.7 and 97.7%, stage III-IV, 94.8 and 92.4%). Median event-free survival (EFS) is 62.3 and 54% respectively (stage I-II, 72 and 64%, stage III-IV, 36.4 and 18.2%). Stage I-II vs III-IV OS (p = < 0.001) and EFS (p = < 0.001) were significant. For stage I-II, 5 year EFS of chemotherapy + RT (83.3%) was superior to chemotherapy alone (60%, p = 0.008). Five year EFS for early favorable (80%), early unfavorable (60%), and advanced (36.4%) was significant (p = < 0.001). Eleven patients (5.5%) had high-grade transformation. Twenty-nine patients underwent HDC auto-SCT, all are alive (28 in remission). 25% of patients had pathologically proved nodal hyperplasia at some point in time. CONCLUSION: OS of NLPHL is excellent and independent of treatment type. EFS is better for chemotherapy + RT than chemotherapy alone. Stem cell transplant in refractory / multiple relapses resulted in excellent disease control. There is a need to identify optimal treatment strategies accordingly to the risk stratification.

Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) version 4 quality of life instrument into Arabic language.

BACKGROUND: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) has been translated from English into several languages. Currently, there is no validated translation of FACT-BMT in Arabic. Here, we are reporting the first Arabic translation and validation of the FACT-BMT. METHODS: The study was approved by the Institutional Research Advisory Council. The Arabic translation followed the standard Functional Assessment of Chronic Illness Therapy (FACIT.org) translation methodology (with permission). Arabic FACT-BMT (50- items) was statistically validated. Cronbach's alpha for internal consistency, Spearman's rank correlation coefficients method for Inter-scale correlations and Principal Component Analysis for factorial construct validity was used. RESULTS: One hundred and eight consecutive relapsed /refractory lymphoma patients who underwent high dose chemotherapy and autologous stem cell transplant were enrolled. There were 68 males (63%) and 40 females (37%) with a median age of 29 years (range 14-62). After Arabic questionnaire pre-testing (Cronbach's alpha 0.744), the study included 108 patients. Cronbach's alpha for the entire FACT-BMT indicated an excellent internal consistency (0.90); range (0.67 to 0.91). Cronbach's alpha for sub-groups of social (0.78), emotional (0.67) and functional wellbeing was (0.88). Cronbach's alpha for bone marrow transplant (0.81), FACT-General (0.89), and FACT- Trial Outcome Index (TOI); (0.91) also revealed excellent internal consistency. Patients had high scores in all domains of quality of life, indicating that most patients were leading a normal life. This translation of FACT-BMT in Arabic was reviewed and approved for submission by the FACIT.org. CONCLUSIONS: Our data reports the first translated, validated and approved Arabic version of FACT-BMT. This will help large numbers of Arabic speaking patients undergoing stem cell/bone marrow transplantation, across the globe.

High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.