Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

We evaluated whether vitamin D insufficiency (VDI; 25(OH)D <20 ng/ml) was associated with adverse outcomes among follicular lymphoma (FL) patients using an observational prospective cohort study of 642 FL patients enrolled from 2002-2012. The median age at diagnosis was 60 years. At a median follow-up of 59 months, 297 patients (46%) had an event (progression, treatment failure), 78 had died and 42 (6.5%) had a lymphoma-related death. VDI was associated with inferior event-free survival (EFS) at 12 months (EFS12, odds ratio (OR)=2.05; 95% confidence interval (CI) 1.18-3.54), overall survival (OS, hazards ratio (HR)=2.35; 95%CI 1.37-4.02), and lymphoma-specific survival (LSS, HR=2.97; 95% CI 1.52-5.80) for the full cohort. Among patients treated with immunochemotherapy (IC), VDI was associated with inferior EFS12 (OR=3.00; 95% CI 1.26-7.13), OS (HR=2.86; 95% CI 1.39-5.85), and LSS (HR=2.96; 95% CI 1.29-6.79). For observed patients, VDI was associated with inferior OS (HR=2.85; 95% CI 1.20-6.76). For other therapies, VDI was associated with inferior OS (HR=3.06; 95% CI 1.01-9.24). Our work is the first to reveal an association of VDI with early clinical failure, and to demonstrate an association of VDI with adverse outcomes among patients who are observed or treated with therapies other than IC. Our findings suggest a potentially modifiable prognostic factor to address in patients with FL.

Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma.

Given the survival advantage, high-dose therapy (HDT) remains the standard of care for patients with multiple myeloma eligible for the procedure. For those undergoing HDT, initial therapy aimed at reducing tumor burden is given prior to stem cell harvest. Various regimens, mostly variations of VAD (vincristine, doxorubicin, dexamethasone), are used for induction therapy. We retrospectively evaluated if single agent dexamethasone would be an effective induction therapy, given that it is the most active drug in these combinations. A total of 35 patients who received induction therapy with dexamethasone alone were compared to a similar group of 72 patients who received VAD as the initial therapy. We found a 63% response rate with dexamethasone compared to 74% with VAD (P=0.25). Including minimal responses, the overall response rate for Dex and VAD was 74 and 86%, respectively (P=0.13). The overall and complete response rates to transplant, respectively, were 97 and 26% for the dexamethasone group and 100 and 39% for the VAD group; P=0.33 and 0.18. No significant differences were observed in the progression-free and overall survival at 1 year post transplant. Single agent dexamethasone appears to be an effective alternative to VAD for induction therapy prior to HDT in myeloma.

High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy.

Autologous stem cell transplant (SCT) improves survival in multiple myeloma (MM) and remains the standard of care for eligible patients. Nearly a third of patients with newly diagnosed MM fail initial therapy aimed at reducing tumor burden preceding SCT (primary refractory). It is unclear if an initial response is important for successful SCT. We evaluated our experience with SCT in 50 patients with primary refractory MM and compared it to 101 patients with chemosensitive disease receiving SCT. The study cohort had a median age of 56 years (range 29-72) consisting of 87 males (58%). A total of 46 patients (92%) in the refractory group and 100 (99%) in the chemosensitive group had a response to transplant (50% or greater reduction in the M-protein). In all, 10 refractory patients (20%) and 35 (35%) in the chemosensitive group achieved a CR (P=0.06). The 1-year estimated progression-free survival from the time of transplant for the refractory group was 70% compared to 83% for the chemosensitive group (P=0.65). The lack of response to initial induction therapy does not appear to preclude a good response to SCT. We recommend that patients with primary refractory MM be offered early SCT.

A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia.

In an earlier study of previously untreated patients with chronic lymphocytic leukemia (CLL), we used a concomitant combination of chlorambucil and 2-chlorodeoxyadenosine and reported overall (OR) and complete (CR) remission rates of 80% and 20%, respectively. After a median follow-up of 5 years, more than 80% of the responders have had a relapse. In the current phase II study of 27 previously untreated patients with CLL, we used a sequential combination of six cycles of intravenous cyclophosphamide (1 g/m2) plus oral prednisone (100 mg/m2 per day for 5 days) followed by two to six cycles of 2-chlorodeoxyadenosine (5 mg/m2 per day for 5 days). The OR and CR rates were 96% and 33%, respectively. After a median follow-up of 29 months, 35% of the responders have had a relapse. Progression-free survival was significantly better in CR patients than in those with partial remission. However, minimal residual disease was phenotypically detected in four of the nine CR patients. Despite the fact that the current OR and CR rates are superior to those seen in a historical cohort treated with a concomitant schedule, a longer follow-up period is needed to assess the durability of these remissions, and a controlled trial is necessary to estimate the impact on overall survival and toxicity.

Efficacy of splenectomy for patients with mantle cell non-Hodgkin's lymphoma.

The purpose of this study was to define the role of splenectomy in patients (pts) with mantle cell lymphoma (MCL) with regard to improving cytopenias and symptoms of splenomegaly. 26 pts with MCL underwent splenectomy between January 1987 and October 1999 and were followed prospectively for hematologic response and operative morbidity and mortality. A positive response was defined at 1 month of follow-up as: a hemoglobin of > or = 1.0 g/dl in a pt with a preoperative value < 11.0 g/dl; or a platelet count of > or = 100 x 10(9)/L in a pt with a preoperative value < 100 x 10(9)/L. A positive hematologic response was achieved in 69.2% of pts with preoperative anemia, 90% with thrombocytopenia, and 50% with both anemia and thrombocytopenia. The peri- and post-operative morbidity were 3.8 and 19.2%, respectively, the operative mortality was 0%. The median duration of hospitalization was six days. Four (15.4%) pts have not required chemotherapy after splenectomy. Three of these four were previously untreated and they have maintained stable disease for eight years after splenectomy without chemotherapy. Eight additional pts did not require chemotherapy for > 13 months after splenectomy. These results suggest that splenectomy may provide durable remission in selected pts with refractory cytopenias or symptoms related to splenomegaly in pts with MCL. There is a subset of pts that have prolonged disease stabilization without the requirement for immediate chemotherapy after splenectomy.

Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial.

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.