Approximately 20% of patients with multiple myeloma (MM) have renal failure at diagnosis, and about 5% are dialysis-dependent. Many of these patients are considered ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) because of a high risk of treatment-related toxicity. We evaluated the outcome of 46 patient with MM and renal failure, defined as serum creatinine >2 mg/dL sustained for >1 month before the start of preparative regimen. Patients received auto-HSCT at our institution between September 1997 and September 2006. Median serum creatinine and creatinine clearance (CrCl) at auto-HSCT were 2.9 mg/dL (range: 2.0–12.5) and 33 mL/min (range: 8.7–63), respectively. Ten patients (21%) were dialysis-dependent. Median follow-up in surviving patients was 34 months (range: 5–81). Complete (CR) and partial responses (PR) after auto-HSCT were seen in 9 (22%) and 22 (53%) of the 41 evaluable patients, with an overall response rate of 75%. Two patients (4%) died within 100 days of auto-HSCT. Grade 2–4 nonhematologic adverse events were seen in 18 patients (39%) and included cardiac arrythmias, pulmonary edema, and hyperbilirubinemia. Significant improvement in renal function, defined as an increase in flomerular filtration rate (GFR) by 25% above baseline, was seen in 15 patients (32%). Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 36% and 64%, respectively. In conclusion, auto HSCT can be offered to patients with MM and renal failure with acceptable toxicity and with a significant improvement in renal function in approximately one-third of the transplanted patients. In this analysis, a melphalan (Mel) dose of 200 mg/m2 was not associated with an increase in toxicity or nonrelapse (Mel) mortality (NRM).

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Sulforaphane (SFN) is a metabolic by product of cruciferous vegetables and is the biologically active phytochemical found in high concentrations in broccoli. It has been studied extensively for its anticancer efficacy and the underlying mechanisms using cell culture and preclinical models. The immediate precursor of SFN is glucoraphanin, a glucosinolate which requires metabolic conversion to SFN. SFN and other notable isothiocyanates, including phenethyl isothiocyanate and benzyl isothiocyanate found in various cruciferous vegetables, have also been implicated to have a chemopreventive role for breast, colon and prostate cancer. In-vitro and in-vivo anti-cancer activity of this class of compounds summarizing the past two decades of basic science research has previously been reviewed by us and others. The present review aims to focus specifically on SFN and its chemopreventive and antineoplastic activity against prostate cancer. Particular emphasis in this communication is placed on the current status of clinical research and prospects for future clinical trials with the overall objective to better understand the clinical utility of this promising chemopreventive nutraceutical in the context of mechanisms of prostate carcinogenesis.

A high risk of regimen-related toxicity with allogeneic hematopoietic stem cell transplantation (allo-HSCT) limits this potentially curative treatment for patients with a left ventricular ejection fraction (LVEF) of ≥50%. We evaluated the frequency of cardiac complications and 100-day nonrelapse mortality (NRM) in 56 patients with a LVEF of ≤45%, who received allo HCTat our institution. The results were retrospectively compared with a matched control group with LVEF of ≥50%, which received an allogeneic stem cell transplantation (allo-SCT). After a median follow-up of 29 months in the study group, grade ≥2 cardiac complications were seen in 7 of 56 (12.5%) patients and cumulative incidence of 100-day NRM was 12.5% with no deaths from cardiac causes. In contrast, after a median follow-up of 49 months in the control group, grade >2 cardiac complications were seen in 19 of 161 patients (11.8%; P = 1.00) and cumulative incidence of 100-day NRM was 14.9% (P =.82). The presence of at least 1 of the 7 pretransplant cardiac risk factors (past history of smoking, hypertension, hyperlipidemia, coronary artery disease, arrhythmia, prior myocardial infarction, and congestive heart failure) was associated with a higher cardiac complication rate in the study group (P = .03). In conclusion, selected patients with a LVEF of ≤45% can safely receive allo-HCT without a significant increase in cardiac toxicity or NRM.

142 Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (E/GEJ) cancer results in a complete pathologic response rate (pCR) of 20-30%. The appearance of favorable microenvironment features (enhanced tumor infiltrating lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest early stage tumors may respond favorably to immune based therapy and in particular to PD-1 blockade when combined with cRT. Methods: In this pilot study, we administered 2 cycles of induction nivolumab (N) q2 weekly prior to standard of care carboplatin/paclitaxel/radiation plus 3 additional cycles of N on week 1, 3 and 5 of cRT. An Ivor-Lewis esophagectomy (E/MIE) was performed 6-10 weeks after the last IO dose. The primary endpoints of the study were safety and feasibility. We also evaluated the pCR, survival and temporal dynamics of T cell receptor clonotypes. Results: Between August 2017 and July 2018, 16 patients were enrolled on study. Induction N and neoadjuvant N combined with cRT in stage II/III E/GEJ cancers has an acceptable toxicity profile and was not associated with delays in surgery. Toxicities of note include steroid responsive grade 3 dermatitis (1/16), grade 3 hepatitis (1/16) and no cases of pneumonitis. To date, 10 patients with E adenocarcinoma have had an E/MIE and the pCR is 4/10 (40%). T cell receptor sequencing of the tumor bed and serial peripheral blood T cells revealed high peripheral representation of tumor-associated T cells. In one notable case, the highest-frequency intratumoral clone decreased in frequency in the peripheral blood upon treatment and rapidly increased after surgical resection, potentially signifying trafficking to the tumor site. Conclusions: Induction N and N combined with cRT has limited side-effects, did not result in surgical delay or enhanced surgical morbidity/mortality and induced a pCR of 40% in stage II/III E/GEJ cancers. Additional efficacy data on the full cohort and more in depth correlative studies will be presented to validate systemic activation of anti-tumor T cell responses. Clinical trial information: NCT03044613.