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.

Impact of Radiation Therapy After High Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients With Relapsed/Refractory Lymphomas: A Single Center Experience.

INTRODUCTION: After high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT), in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), involved field radiation therapy (RT) for consolidation and residual/progressive disease (PD) eradication is a common practice. MATERIALS AND METHODS: Retrospective single-institution cohort analysis to evaluate the impact of early RT after HDC auto-SCT. RESULTS: Between 1996 and October 2019, 153 patients (43 DLBCL, 110 HL) underwent RT after HDC auto-SCT. Males 95 (62%), females 58 (38%), median age 24 years. Indications for RT was consolidation 65%: residual disease eradication 16%: and PD eradication 19%. For DLBCL, the median overall survival (OS) for the above indications was not reached (NR):NR:2 months and the KM 5-year OS was 72.6%:64.3%:12.5% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .88) but both were superior to PD disease eradication (P ≤ 000 and P = .005 respectively). For HL, indication for RT was, 54%:23%:24% respectively. The median OS was NR:NR:28.8 months and KM 5-year OS was 82.3%:78%:30% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .98) but both were superior to the PD eradication group (P ≤ 000). RT was well tolerated with no significant long-term toxicity. CONCLUSION: Post HDC auto-SCT RT was well tolerated. DLBCL and HL patients with residual disease treated with the RT had similar long-term survival as those who received RT for consolidation. RT failed to improve the poor survival in patients with post-HDC auto-SCT PD.

A Case of Diffuse Large B-cell Lymphoma with Cardiac Involvement Incidently Diagnosed on Cardiac Imaging.

Cardiac lymphomas, either primary or secondary, are mostly of B-cell lineage; among which, diffuse large B-cell lymphoma (DLBCL) is the most common. Secondary involvement of the heart is usually a late manifestation of disseminated lymphoma. Patients may be asymptomatic or may have non-specific symptoms, particularly when cardiac involvement is not extensive. A 22-year male patient presented with four months' history of progressive enlargement of left cervical lymph nodes with intermittent fever along with dysphagia and left ear pain. Positron-emission tomography (PET)/computed tomography (CT) scan revealed abnormal fluorodeoxyglucose (FDG) uptake in multiple systemic locations including inferior wall of the myocardium. Subsequently, cardiac MRI showed left ventricular posterolateral wall abnormal area of delayed enhancement, corresponding to the FDG uptake on PET CT scan. Patient had remission after completion of standard chemotherapy protocol for the management of DLBCL with acceptable toxicity. Key Words: Diffuse large B-cell lymphoma (DLBCL), Secondary, Heart, Chemotherapy.

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.

Risk of hematological malignancies in the families of patients treated for nodular lymphocyte-predominant Hodgkin lymphoma.

BACKGROUND: Familial clustering of lymphoid and/or hematological malignancies (FHM) provides an opportunity to study the responsible genes. The data is limited in patients with lymphoid and hematological malignancies. METHODS: The lymphoma database was used to identify patients seen in our institution from 1998 to 2019 with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We studied FHM by collecting detailed history of any malignancy in the family (FM). RESULTS: Two hundred NLPHL patients were identified. Contacting was not possible in 30 patients due to no response to the phone calls (22) and death [1]. 170/200 patients were interviewed; represented 167 families (3 patients with a family member with NLPHL). These 170 patients provided information about 8225 family members. These 167 families had a total of 329 family members with 334 malignancies (including 167 NLPHL patients and 5 members with 2 malignancies each). Of these 167 patients, 77 (46.1%) had no FM while 90 (53.9%) patients had a positive FM; 162 family members with 167 malignancies. Among these 167 families, 31 families (18.6%) had members with FHM +/- solid cancers. These 31 families had 35 family members (25 males:10 females) with 16 lymphomas: diffuse large B cell lymphoma [2], follicular center cell lymphoma [3], chronic lymphocytic leukemia/small lymphocytic lymphoma [3], non-Hodgkin lymphoma [2], classical HL [2], and NLPHL [4]. Total of 8 leukemia: acute lymphoblastic leukemia [4], acute myeloid leukemia [3], and leukemia - no subtyping [5]. These 35 FHM members are 1st [6], 2nd (16), and 3rd [7] degree relatives of 31 NLPHL patients. There are 4 families with NLPHL in family members; all these 8 NLPHL patients are male and are alive. The median total number of 1st + 2nd +3rd degree members are 81. The decrease in the age of diagnosis from 1st generation to the 2nd generation (anticipation) was noted in 13/17 patients; 2nd generation median age at diagnosis was 29.7 years vs 1st generation age 53 years (developed malignancy 23.3 years earlier). CONCLUSION: FHM is frequent in NLPHL. This study provided us many important insights for planning future studies in terms of interviewing technique, time, and resource allocation and genetic testing.

Hodgkin lymphoma involving extranodal sites in head and neck: report of twenty-nine cases and review of three-hundred and fifty-seven cases.

INTRODUCTION: Hodgkin lymphoma (HL) involving the Waldeyer's ring (WR) and other extranodal head and neck sites are rare. We report our experience and PubMed literature review. METHODS: Retrospective single institution cohort study using lymphoma data base and PubMed literature search using twenty-six various search terms. RESULTS: Twenty-nine patients were treated in our institution (1975-2018). Male:Female 22:7, median age at diagnosis 33 years (15-64), stages I-II:III-IV 25:4. Sites were nasopharynx (10), tonsil (9), parotid (5), mandible (2) and others (3). 20/29 patients received radiation therapy, 22/29 received chemotherapy. Ten years overall-survival and progression-free survival are 92% and 66% respectively. PubMed search showed 8766 citations and identified 357 patients including our patients. Male:Female 199:131, median age 45 years (5-89). Stages I-II in 286 (80%). Involvement was nasopharynx 109 (30.5%), tonsil 67 (18.8%), parotid 58 (16.2%), thyroid 45 (12.6%), adenoid 10 (2.8%), mandible 10 (2.8%) and others in 58 (16.2%). Pathology: mixed cellularity 99 (27.7%), nodular sclerosis 88 (24.6%), nodular lymphocyte-predominant 56 (15.7%), lymphocyte rich 25 (7%), classical-HL-not otherwise specified 16 (4.5%) and lymphocyte depleted 7 (2%) patients. Treatment details are available for 233 patients; 165 (46%) received radiation therapy, 137 (38%) chemotherapy. Complete remission in 208 (58%), progressive disease 14 (4%), no information 135 (38%). Overall, treatment failure in 54 (15%). Thirty (8.4%) have died; 21 disease related. KM overall-survival at 5 and 10 years was 88.5% and 77.6% respectively. CONCLUSION: This largest report showed that HL involving extranodal head and neck sites is not very uncommon and has excellent prognosis.

Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional study of adult patients by ILROG.

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.

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.

Survival analysis of patients with Hodgkin lymphoma who failed high dose chemotherapy and autologous stem cell transplant.

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.

Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults.

Changing trends of adult lymphoma in the Kingdom of Saudi Arabia - comparison of data sources.

BACKGROUND: Lymphoma is one of the most common malignancies affecting the young Saudi population. This disease has diversified pathologies and clinical stages that necessitate well optimized clinical management. Regular updates of epidemiological behavior of lymphoma from various parts of the world are available but studies from the Kingdom of Saudi Arabia (KSA) in this field are not consistent. OBJECTIVES: The aim of this study was to investigate the current trends in presentation and distribution of lymphoma with special reference to incidence and mortality, gender, age, histopathological subtypes, and clinical stages at King Faisal Specialist Hospital and Research Centre (KFSH and RC). MATERIALS AND METHODS: Our study included lymphoma data from Saudi Cancer Registry, and relative comparison against KFSH and RC tumor registry data, Gulf country data and International Agency for Research on Cancer data. RESULTS: Common tumors in the West (lung, colon, and prostate) were found to be much less frequent in KSA while leukemia, lymphoma and thyroid cancers were more common. Non-Hodgkin Lymphoma (NHL) ranked 3rd most common cancer with age-adjusted incidence of 6/100,000. Estimated age adjusted mortality was 4/100,000 in KSA. There was a peak rise in incidence of lymphoma in 1997-2007. Most common NHL was diffuse large B cell lymphoma at KFSH and RC. A total of 434 cases were diagnosed in 5 years with 55% of them at advanced stage and 35% demonstrating bulky disease and high risk. KFSH and RC registered 35% of Hodgkins and 21% of total NHL identified in entire Saudi Cancer Registry, 2009. CONCLUSIONS: Results of this study are very unique, and reveal diverse trends. The findings provide valuable insights in the understanding of current epidemiological features of lymphoma in this part of the world.

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.

The utility of online haemodiafiltration in methotrexate poisoning.

Summary We report a case of a 56-year-old woman with a high-grade diffuse large B-cell lymphoma who unexpectedly developed toxic plasma levels of methotrexate (MTX) following the first cycle of rituximab-cyclophosphamide, hydroxydanorubicin, oncovin, prednisolone (R-CHOP) with a high-dose MTX chemotherapy protocol. She also developed non-oliguric acute kidney injury secondary to MTX nephrotoxicity. We elected to treat her with online-haemodiafiltration (HDF) and this proved to be efficient with a dramatic response. Rapid clearance of MTX to therapeutic levels was possible within three sessions. Prompt therapy with high-volume online-HDF is an effective choice for rapid MTX clearance and swift reversal of MTX nephrotoxicity.

Upper aero-digestive tract lymphomas presenting as polypoidal/pedunculated lesions: case report and review of literature.

AIM: To describe a case of diffuse large B cell lymphoma (DLBCL) presenting as a pedunculated/polypoidal mass in upper aero-digestive tract and to review pertinent literature. METHODS: Using Pubmed advanced search, case reports and literature were reviewed for this condition. RESULTS: A 16 year old female presented with history of shortness of breath when lying down, voice change, progressing odynophagia and feeling of throat lump. Direct visualization showed flower like pedunculated mass, attached to the left lateral oropharyngeal wall. Excision of this mass showed DLBCL and no disease anywhere. She received four cycles of Rituximab + CHOP and is disease-free for 4 years. Only 21 cases of pedunculated upper aero-digestive tract lymphomas have been reported in literature. Median age 53 years (16-90 years), males 80 %, females 20 %, localized disease (65 %). Common sites were endobronchial polypoid lesion (7 cases), nasal polyps (7), nasopharyngeal polyps (2), nose and paranasal sinus (1), laryngeal polyp (2) and one each as gum, esophagus and oropharyngeal (current case) polyp. Pathology showed aggressive lymphoma in 94 %. CONCLUSION: DLBCL as an extranodal pedunculated lesion in the oropharynx is very rare. Careful pathological evaluation is essential for these lesions for proper diagnosis.

The current lymphoma classification: new concepts and practical applications triumphs and woes.

The World Health Organization (WHO) classification of lymphomas updated in 2008 represents an international consensus for diagnosis of lymphoid neoplasms based on the recognition of distinct disease entities by applying a constellation of clinical and laboratory features. The 2008 classification has refined and clarified the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. Rather than being a theoretical scheme this classification has used data from published literature. Recent knowledge of molecular pathways has led to identification and development of new diagnostic tools, like gene expression profiling, which could complement existing technologies. However, some questions remain unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors. In general, practical considerations and economics preclude a heavily molecular and genetic approach. The significance of early or precursor lesions and the identification of certain lymphoid neoplasms is less clear at present, but understanding is evolving. The borderline categories having overlapping features with large B-cell lymphomas, as well as some of the provisional entities, are subject to debate and lack consensus in management. Lastly, the sheer number of entities may be overwhelming, especially, for the diagnosing pathologist, who do not see enough of these on a regular basis.

Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody (rituximab).

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders.

Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma.

BACKGROUND: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). METHODS: All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded (4 had WBI<40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose>40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI. RESULT: Of 52 patients analyzed for outcome, 36 had WBI (dose>40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. x22%, p=.029). Median follow up was 12.83±6.4 months. The hazard ratio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60 years), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs multifocal tumor and dose of radiation therapy (<50 Gy vs. >50 Gy) failed to identify any prognostic factor. CONCLUSION: This retrospective comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome.