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.

High-dose chemotherapy and autologous stem cell transplant in adolescent patients with relapsed or refractory Hodgkin's lymphoma.

Fifty-eight adolescent patients with relapsed or primary refractory Hodgkin's lymphoma underwent high-dose chemotherapy (HDC) and autologous SCT (ASCT). The median age at ASCT was 17 years (range 14-21). The disease had relapsed in 24 patients (41%) and was refractory to initial chemotherapy in 34 (59%). ESHAP salvage chemotherapy before ASCT resulted in 88% response. After ASCT, complete remission (CR; including CR-unconfirmed) was seen in 41 patients (71%) and partial remission in 7 (12%). The overall response rate was 83%. One patient did not respond and nine (15%) had progressive disease. Three more patients achieved CR after consolidative radiation post-ASCT. There was no transplant-related mortality. At a median follow-up of 43 months from ASCT, 31 patients (53%) are alive in CR, 5 (9%) are alive with disease and 22 (38%) have died (21 from disease and 1 unrelated). The actuarial probabilities of event-free and overall (OS) survival are 45 and 55% at 11 years. The only negative prognostic factor for OS was the presence of B symptom at relapse or progression (11-year OS 27 vs 60%, P=0.003).

High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and research center experience.

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis) with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post-ASCT evaluation showed response in 50 patients (76%), complete response (CR) in 37 (56%), partial response in 14 (21%), no response or stable disease in three (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and 57 months, respectively. EFS and overall survival (OS) are 36 and 64%, respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

Primary refractory Hodgkin's lymphoma: outcome after high-dose chemotherapy and autologous SCT and impact of various prognostic factors on overall and event-free survival. A single institution result of 66 patients.

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

ESHAP + fixed dose G-CSF as autologous peripheral blood stem cell mobilization regimen in patients with relapsed or refractory diffuse large cell and Hodgkin's lymphoma: a single institution result of 127 patients.

From 1996 to November 2004, 131 consecutive patients with relapsed or refractory diffuse large cell lymphoma (DLCL) and Hodgkin's lymphoma (HD) received ESHAP as mobilization chemotherapy before autologous peripheral blood stem cell transplant (ASCT). Patients received fixed dose G-CSF 300 microg SC bid starting 24-36 h after finishing mobilizing ESHAP. In all, four patients failed mobilization and are excluded. Characteristics of 127 patients: 68 males: 59 females. DLCL 49: HD 78. Initial stage I:II:III:IV:unknown was 15:34:33:42:3. Median age at ASCT 26 years. Median prior chemotherapy cycles were six [<6 (17 patients), 6-8 (90 patients), >8 (20 patients)]. Median ESHAP cycle used as mobilizer was third. Patients required 1, 2, 3, 4 apheresis were 93:25:8:1. Median total CD34+ cells/kg collected were 6.9 x 10(6) (DLCL 5.17 x 10(6) and HD 7.6 x 10(6)), patients weighing < or = 70 kg (93 patients) 6.54 x 10(6) and >70 kg (34 patients) 7.44 x 10(6) (P = 0.59), one apheresis (93 patients) 8.6 x 10(6)/kg and >1 apheresis (34 patients) 4.5 x 10(6) (P = 0.001). We conclude that ESHAP and G-CSF 300 microg SC bid is an effective mobilizing regimen even in patients >70 kg and most patients require only 1-2 apheresis.

Distal margin requirements after preoperative chemoradiotherapy for distal rectal carcinomas: are < or = 1 cm distal margins sufficient?

BACKGROUND: Sphincter-sparing alternatives to abdominoperineal resection (APR) in the treatment of rectal cancer often are underused out of concern for inadequate distal margins and local failure. The present study addresses whether sphincter-sparing techniques with distal margins < or = 1 cm adversely influence oncological outcome in patients given preoperative chemoradiotherapy. METHODS: Thirty-seven patients with rectal cancer < or = 8 cm from the anal verge were enrolled in the study. Preoperative external beam radiotherapy (5400 Gy) was administered together with continuous infusion of 5-fluorouracil (300 mg/m2/day). Surgical resection was performed in 36 patients with pathological assessment of tumor response and margins. Patients with sphincter-sparing resection and distal margins > 1 cm or < or = 1 cm and those who underwent APR were compared. RESULTS: Thirty-six patients completed preoperative chemoradiotherapy, with successful sphincter-preservation in 28 patients. At a median follow-up of 33 months, there were 12 recurrences overall, which included 11 distant failures and four pelvic failures. Disease-free survival (DFS) was not different between those who had an APR compared with sphincter-sparing resection with distal margins < or = 1 cm. DFS was worse (P < .02) when radial margins were < or = 3 mm compared with > 3 mm. CONCLUSIONS: Sphincter preservation is feasible in more than 75% of patients with tumors < or = 8 cm from the anal verge after preoperative chemoradiotherapy. Sphincter-sparing surgery with distal margins < or = 1 cm can be used without adversely influencing local recurrence or DFS. Limited radial margins (< or = 3 mm), however, are associated with increased disease recurrence.

A case of biliary carcinoid presenting with pancreatitis and obstructive jaundice.

A 43-yr-old man presented to the clinic with abdominal pain, jaundice, nausea, and vomiting and weight loss over a 6-month period. Physical exam was unrevealing other than mild epigastric tenderness. A computed tomographic scan of the abdomen revealed a mass in the head of the pancreas, which was resected at laparotomy by a Whipple's procedure. The histology showed a biliary tract carcinoid tumor. The patient had normal hydroxy-indole-acetic acid (HIAA) levels throughout. There has been no evidence of disease or tumor recurrence at 3.5 yr of follow up.

Primary extra-nodal lymphoma of the urinary bladder.

Primary non-Hodgkin's lymphoma of the urinary bladder is rare. Only a few cases have been reported. We report the case of a woman with non-Hodgkin's lymphoma of urinary bladder and review the literature.