High-dose chemotherapy and autologous stem cell transplantation for relapsed or refractory nodular lymphocyte predominant Hodgkin lymphoma.

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 (1996­2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15­58 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 (6­124 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. Kaplan­Meier 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.

Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age <40 years at auto-SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT.

Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin's lymphoma: outcome after high-dose chemotherapy and auto-SCT.

Hodgkin's lymphoma (HL) patients with positive (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) post salvage chemotherapy or before high-dose chemotherapy and auto-SCT (HDC ASCT) have inferior outcomes. We reviewed 21 prognostic factors before salvage chemotherapy (at relapse/progression) and integrated post salvage FDG-PET results to develop a prognostic model for post HDC ASCT outcome. We used Fine and Gray method for competing risk analysis and regression model for risks assessment and outcome. One hundred and forty-one patients had post salvage FDG-PET before HDC ASCT (median age 25.5 years); male/female 55%:45%, relapsed/refractory 43%:57%, median follow-up 33 months. Multivariate analysis identified HL International Prognostic Score 3 (P=0.001; hazard ratio (HR): 3.7 (1.6-8.3)) and post salvage positive FDG-PET (P=0.011; HR: 3.4 (1.3-8.9)) with higher hazard of disease-specific death (model P=0.0001). Cumulative incidence of disease-specific death with 0, 1, 2 risk factors was 7%:29%:52%, respectively (P=0.00003). For disease-specific event (persistent, progressive or relapsed disease), mediastinal involvement (P=0.024; HR: 2.7 (1.14-6.5)), B symptoms (P=0.027; HR: 2.1 (1.09-4.2)) and positive post salvage FDG-PET (P=0.001; HR: 3.3 (1.7-6.7)) were significant (model P=<0.00001). Cumulative incidence of disease-specific event with 0, 1, 2, 3 risk factors was 8%:31%:50%:75%, respectively (P=0.0000006). Patients with higher scores have higher risk of treatment failure. They are potential candidates for newer therapies along with HDC ASCT.

Pre-transplant (18)F-fluorodeoxyglucose positron emission tomography-based survival model in patients with aggressive lymphoma undergoing high-dose chemotherapy and autologous SCT.

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) documented response after salvage chemotherapy has been reported to impact survival in patients with aggressive non-Hodgkin's lymphoma, especially diffuse large B cell lymphoma (DLBCL) undergoing high dose chemotherapy and autologous SCT (HDC auto-SCT). We reviewed the impact of 19 different prognostic/predictive factors before salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC auto-SCT outcome. The Fine and Gray method for competing risk analysis and a regression model was used to assess the risk associated with different factors on outcome. Fifty-five patients had FDG-PET after salvage chemotherapy; male 65%, female 45%, relapsed 55%, refractory 45%, DLBCL 82%, T cell lymphoma 18%, median age at auto-SCT 40 years, median follow-up 42.4 months. Multivariate analysis identified only positive FDG-PET (P=0.04) and mediastinal involvement (P=0.05) with higher hazard rate of disease-specific death (model P=0.008) but only positive FDG-PET (P=0.01) for disease-specific events (persistent, progressive or relapsed disease). Cumulative incidence of disease-specific death for patients with 0, 1 and 2 risk factors was 5, 30 and 62%, respectively (P=0.01). Our model is significant and showed an increasing risk of failure with mediastinal involvement and post-salvage positive FDG-PET.