F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma.

Total lymphoid irradiation (TLI) followed by high-dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high-dose chemotherapy and aHSCT. Pre-transplant fludeoxyglucose positron emission tomography (FDG-PET) studies were scored on the 5-point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10-year progression-free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5-year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long-term survival rates for patients with relapsed/refractory HL, including those with high-risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.

Tipifarnib as maintenance therapy did not improve disease-free survival in patients with acute myelogenous leukemia at high risk of relapse: Results of the phase III randomized E2902 trial.

PURPOSE: Despite the achievement of complete remission with chemotherapy in patients with acute myeloid leukemia (AML), relapse is common and the majority of patients will die of their disease. Patients who achieve a remission after refractory or relapsed disease as well as elderly patients have a very high rate of relapse even if they achieve a complete remission. A phase 3 randomized ECOG-ACRIN-led intergroup study was conducted to determine whether post-remission therapy with the farnesyl transferase inhibitor, tipifarnib (R115777), improved the disease-free survival (DFS) of adult patients with AML in complete remission (CR), at high risk for relapse. PATIENTS AND METHODS: Adult patients with AML in remission after salvage therapy and/or over age 60 in first remission were enrolled in this study. They were randomly assigned to treatment with tipifarnib or observation (control). The primary objective was to compare the disease-free survival (DFS) between the two arms based on intention to treat, which includes all randomized patients. RESULTS: One hundred and forty-four patients were enrolled on the study. Median DFS was 8.9 vs 5.3 months, for tipifarnib vs observation (one-sided p = 0.026) and did not cross the pre-specified boundary to call the study positive. For the 134 eligible patients, median DFS was 10.8 vs 5.3 months for those randomized to tipifarnib vs observation (one-sided p = 0.008). Moreover in an ad hoc evaluation of all women (n = 71) median DFS was 12.1 vs 3.9 months for tipifarnib vs observation (one-sided p = 0.0004) while median OS was 26.5 vs 8.4 months respectively (one-sided p = 0.001). CONCLUSION: This study was not able to demonstrate a benefit to tipifarnib as maintenance therapy in patients with AML in remission. While subsets of patients may indeed benefit, additional studies would be needed to elucidate that benefit which is unlikely given that other seemingly better options have since become available.

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up.

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.

Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98).

Waldenström macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma that strongly expresses CD20 on the cell surface. This study was undertaken to determine the response rate of patients with untreated or previously treated WM to the monoclonal antibody rituximab, which is directed against CD20+ expressed by B-cell lymphomas. Thirty-four untreated and thirty-five previously treated patients received rituximab 375 mg/m2 weekly for 4 consecutive weeks by intravenous infusion on days 1, 8, 15, and 22. Sixty-nine patients were evaluable for response; 19 (27.5%) achieved an objective response and 17 (24.6%) achieved a minor response. The overall response rate was 52.2% (90% CI [41.6%, 62.6%]). Of previously untreated patients 35.3% vs. 20% of previously treated patients achieved an objective response. Median response duration was not significantly different between previously untreated (27 months) and previously treated patients (not reached, P = 0.8). Rituximab produced objective or minor responses in 52.2% of patients and is an active agent in the treatment of WM. Grade 4 toxicity was seen in 11%.

Effect of an electronic health record on the culture of an outpatient medical oncology practice in a four-hospital integrated health care system: 5-year experience.

The electronic health record (EHR) was adopted into the NorthShore University HealthSystem, a four-hospital integrated health system located in suburban Chicago, in 2003. By 2005, all chemotherapy and medicine order entry was conducted through the EHR, completing the incorporation of a fully paperless EHR in our hospital-based oncology practice in both the inpatient and outpatient settings. The use of the EHR has dramatically changed our practice environment by improving efficiency, patient safety, research productivity, and operations, while allowing evaluation of adherence to established quality measures and incorporation of new quality improvement initiatives. The reach of the EHR has been substantial and has influenced every aspect of care at our institution over the short period since its implementation. In this article, we describe subjective and objective measures, outcomes, and achievements of our 5-year EHR experience.

Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic stem cell transplantation.

Low CD34 + cell doses increase allograft-related mortality and very high doses increase the risk of graft-versus-host disease. The optimum CD34 + cell dose remains undefined. The effect of the CD34 + cell dose based on ideal weight was analyzed in 130 patients with hematologic malignancies undergoing reduced-intensity allogeneic blood cell transplantation in the context of factors known to affect the outcome: chemosensitivity, donor age, lactate dehydrogenase (LDH), human leukocyte antigen (HLA) match, performance status, and platelet count. The survival of patients receiving >8 x 10(6)/kg CD34 + cells was not significantly different from those receiving <6. The outcome of those receiving 6-8 x 10(6)/kg CD34 + cells was significantly better than the rest. This superiority was confirmed in multivariable analysis. Among patients receiving 8) needs further confirmation.

Oxaliplatin-related acute myelogenous leukemia.

A 56-year-old woman diagnosed with a poorly differentiated cecal adenocarcinoma with metastases to ovaries, omentum, and sigmoid colon went into remission after 12 cycles of infusional 5-fluorouracil, luecovorin, and oxaliplatin (FOLFOX-4 regimen). Thirteen months later, a pelvic recurrence was diagnosed, and the patient received nine cycles of FOLFOX-6 plus bevacizumab, resulting in a clinical complete response but the development of pancytopenia. Bone marrow biopsy was consistent with therapy-related acute myelogenous leukemia. Chromosome analysis showed structural rearrangements with partial deletions of the long arms of chromosomes 5, 7, 20, and 21, as well as trisomy of chromosome 8 and losses of chromosomes 3 and 11. Induction chemotherapy led to remission, but the patient died two months later from complications of colon cancer progression. It is likely that the leukemia was related to the oxaliplatin administration.

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma.

PURPOSE: Anaplastic oligodendroglioma is a chemosensitive glial neoplasm. To improve disease control and postpone cranial radiotherapy, we designed a phase II study of intensive procarbazine, lomunstine and vincristine followed by high-dose thiotepa with autologous stem cell rescue for patients with newly diagnosed anaplastic or aggressive oligodendroglioma. PATIENTS AND METHODS: Sixty-nine patients with a median age of 42 (range: 18-67) and a median Karnofsky Performance Score of 90 (range: 70-100) were enrolled. Sixteen patients had a prior diagnosis of low-grade oligodendroglioma and 16 had mixed oligoastrocytoma pathology. Only patients with demonstrably chemosensitive enhancing tumors or those free of enhancing tumor after surgery and induction therapy were eligible to receive high-dose thiotepa. RESULTS: Thirty-nine patients (57%) completed the transplant regimen; their estimated median progression-free survival is 69 months and median overall survival has not been reached. Twelve transplanted patients (31%) relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with relapse; however, persistent non-enhancing tumor at transplant conferred an increased risk of relapse (p = 0.028). The transplant regimen was well-tolerated; median hospital stay was 20 days (range: 7-43) with a median time to ANC and platelet engraftment of 10 days. Thirty patients (43%) did not receive high-dose thiotepa because of stable or progressive disease (n = 21), excessive toxicity (n = 4), refusal of further therapy (n = 2), failure to obtain insurance coverage (n = 2), or other (n = 1). No treatment-related or long-term neurotoxicity was seen in the transplanted patients. CONCLUSIONS: High-dose chemotherapy with stem cell rescue as initial treatment for anaplastic oligodendroglioma is feasible and associated with prolonged tumor control in some patients.