Unchecked immunity: a unique case of sequential immune-related adverse events with Pembrolizumab.

BACKGROUND: Immune checkpoint inhibition has dramatically transformed the treatment of malignant melanoma. With increasing use, their unique spectrum of immune-mediated toxicity has become apparent. CASE PRESENTATION: We describe a case of sequential immune-related adverse events (irAEs) in a patient with metastatic melanoma treated with single-agent anti-programmed cell death-1 (PD-1) therapy, pembrolizumab. Although numerous cases of irAEs have been reported, sequential multi-organ involvement, including progressive atopic dermatitis, vitiligo, autoimmune nephritis, autoimmune hepatitis, and autoimmune encephalitis after cessation of therapy, has not been previously documented. CONCLUSIONS: Immunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.

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.

Gestational trophoblastic neoplasia: treatment outcomes from a single institutional experience.

PURPOSE: To report the outcomes of gestational trophoblastic neoplasia (GTN) at a single institution and to determine the factors affecting response to chemotherapy and survival. METHODS/PATIENTS: From 1979-2010, we retrospectively reviewed the data of 221 patients treated at our center. GTN Patients were assigned to low-risk (score ≤6) or high-risk (score ≥7) based on the WHO risk factor scoring system. Overall survival (OS) probabilities were estimated using Kaplan-Meier method. Logistic regression was applied to study the impact of different factors on the response to initial therapy. RESULTS: Patients' OS rate was 97 %. Median age at diagnosis was 37 year. 131 (59 %) patients had low-risk and 88 (40 %) cases had high-risk GTN. Complete remission rates to initial chemotherapy in low-risk group were 53 % and 87 % for single-agent methotrexate or dactinomycin, respectively. In high-risk group, 94 % achieved complete remission to initial chemotherapy with etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO). Etoposide, cisplatin, and dactinomycin as primary therapy in high-risk patients was successful in 70 %, while bleomycin, etoposide, and cisplatin (BEP) was successful in 53 % of cases. Salvage chemotherapy, surgical intervention or radiation therapy resulted in overall complete remission of 90 % in low-risk and 73 % in high-risk groups. Factors associated with resistance to initial chemotherapy were advanced-stage III/IV (p = 0.005), metastatic site other than lung or vagina (p = 0.005) and high-risk prognostic score (p = 0.05). OS was significantly influenced by the type of antecedent pregnancy (molar 98 % vs. others 93 %; p = 0.04), FIGO stage (I, II 100 % vs. III, IV 94 %; p = 0.02), score (low-risk 100 % vs. high-risk 92 %; p = 0.01), and site of metastasis (lung/vagina 98 % vs. others 85 %; p = 0.002). CONCLUSIONS: GTNs have excellent prognosis if properly treated at experienced centers. Single-agent dactinomycin seems more effective for low-risk GTN. EMA-CO remains the preferred primary treatment regimen for high-risk group. The excellent outcome reflects the success of salvage therapy.

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.

Gestational trophoblastic neoplasia: treatment outcomes from a single institutional experience

Purpose: To report the outcomes of gestational trophoblastic neoplasia (GTN) at a single institution and to determine the factors affecting response to chemotherapy and survival. Methods/Patients: From 1979–2010, we retrospectively reviewed the data of 221 patients treated at our center. GTN Patients were assigned to low-risk (score ≤6) or high-risk (score ≥7) based on the WHO risk factor scoring system. Overall survival (OS) probabilities were estimated using Kaplan–Meier method. Logistic regression was applied to study the impact of different factors on the response to initial therapy. Results: Patients’ OS rate was 97 %. Median age at diagnosis was 37 year. 131 (59 %) patients had low-risk and 88 (40 %) cases had high-risk GTN. Complete remission rates to initial chemotherapy in low-risk group were 53 % and 87 % for single-agent methotrexate or dactinomycin, respectively. In high-risk group, 94 % achieved complete remission to initial chemotherapy with etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO). Etoposide, cisplatin, and dactinomycin as primary therapy in high-risk patients was successful in 70 %, while bleomycin, etoposide, and cisplatin (BEP) was successful in 53 % of cases. Salvage chemotherapy, surgical intervention or radiation therapy resulted in overall complete remission of 90 % in low-risk and 73 % in high-risk groups. Factors associated with resistance to initial chemotherapy were advanced-stage III/IV (p = 0.005), metastatic site other than lung or vagina (p = 0.005) and high-risk prognostic score (p = 0.05). OS was significantly influenced by the type of antecedent pregnancy (molar 98 % vs. others 93 %; p = 0.04), FIGO stage (I, II 100 % vs. III, IV 94 %;p = 0.02), score (low-risk 100 % vs. high-risk 92 %; p = 0.01), and site of metastasis (lung/vagina 98 % vs. others 85 %; p = 0.002). Conclusions: GTNs have excellent prognosis if properly treated at experienced centers. Single-agent dactinomycin seems more effective for low-risk GTN. EMA-CO remains the preferred primary treatment regimen for high-risk group. The excellent outcome reflects the success of salvage therapy (AU)

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