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A letter to the editor in response to the article "Transplant related outcomes in patients with hematopoietic stem cell transplant with Clostridium difficile associated diarrhea," that was published in a previous issue of the journal is presented.

This study evaluated if measures of psychological well-being, including coping style are associated with advance care planning (ACP). Data were from the HEMA-COMM study, a prospective observational study of physician-patient communication in patients with hematologic malignancies. ACP was defined as having a living will, having a health care proxy, discussing life support with family or friends, and discussing life support with a doctor or nurse. 293 patients participated: only 45 (15%) had all the elements of ACP, 215 (73%) had at least 1 element of ACP, while 33 (11%) did not engage in ACP. In multivariate analysis, specific coping styles but not other measures of psychosocial well being were associated with having written ACP. Verbal ACP was associated with patient-reported health and physician estimate of life expectancy. Our study suggests that tailoring ACP discussions to a patient’s coping style may increase engagement in ACP.

An introduction is presented in which the editor discusses various articles within the issue on topics including risk factors associated with deaths from hematopoietic stem cell transplantation (HSCT), a case-control analysis on HSCT patients, and relapse of the HSCT.

Abstract: A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days −11, −8, −5, and −2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m2) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day −11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m2 but it was later decreased to 1 mg/m2 because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to evaluate the standard outpatient dose of 131-Iodine tositumomab (75 cGy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell rescue for the treatment of chemotherapy-sensitive relapsed or refractory, or high-risk first complete remission (CR) patients with diffuse large B cell non-Hodgkin''s lymphoma (DLBCL). Forty patients with chemotherapy-sensitive persistent or relapsed or high/intermediate or high international prognostic index DLCBL were treated in a phase II trial combining 75 cGy 131-Iodine tositumomab with high-dose BEAM followed by autologous stem cell transplantation. The CR rate after transplantation was 78%, and the overall response rate was 80%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 6 years (range, 3-10 years), the 5-year overall survival (OS) was 72% (95% confidence interval [CI], 55%-83%), and the 5-year progression-free survival (PFS) rate was 70% (95% CI, 53%-82%). The PFS and OS were encouraging in this group of chemotherapy-sensitive persistent, relapsed, or high-risk patients with DLBCL. A follow-up phase III trial with 131-Iodine tositumomab/BEAM vs rituximab/BEAM was planned based on this information. [Copyright &y& Elsevier]

The outcomes for 162 patients with diffuse large B-cell lymphoma treated with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like regimen who obtained a complete remission and who subsequently relapsed after ≥5 years of remission (late relapse, N = 30), or <5 years of remission (early relapse, N = 132), were compared. The late relapsing patients had better prognostic characteristics at diagnosis, such as stage I/II disease (73% vs. 49%, P = 0·04), a normal lactic dehydrogenase (77% vs. 48%, P = 0·01), and a Karnofsky performance score of ≥80 (100% vs. 86%, P = 0·01). The 3-year survival after relapse was better in late relapsing patients (48% vs. 25%, P = 0·03), but the survival at 5 years (32% vs. 20%) and 10 years (13% vs. 14%) after relapse was not different. A multivariate analysis of factors predicting survival after relapse found age ( P < 0·0001) and presence of B-symptoms ( P = 0·03) to predict survival, but not early versus late relapse. A small percentage of the late relapsing patients can have a prolonged second remission. However, the overall survival from the time of relapse was not different between early and late relapsing patients with most succumbing to lymphoma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous meta-analysis on three drugs combination for treatment of advanced non-small cell lung cancer (NSCLC) did not demonstrate an improvement in survival, however many of the trials included in this meta-analysis used older and less effective cytotoxic drugs. We conducted this analysis to compare the relative efficacy of third generation triplet therapy with that of standard double therapy in the treatment of advanced NSCLC. Methods: A MEDLINE search was performed using the search terms “lung cancer” and “randomized trials”. Trials not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel, docetaxel, vinorelbine, gemcitabine) were excluded. Pooled odds ratios (OR) for the objective response and toxicity rates were calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios of individual study. Results: We analyzed six randomized comparative trials involving 1932 patients. Patients receiving triplet therapy had a significantly higher response rate (OR: 1.33; 95% CI, 1.50–2.23; P <0.001). Incidence of grade III/IV hematological toxicity was higher with triplet therapy. Non-hematological toxicities, with the exception of neuropathy, were similar. Median survival of triplet therapy was not significantly different from doublet (MR: 1.10; 95% CI: 0.91–1.35; P =0.059). Conclusions: Triplet therapy with third generation cytotoxic drugs is associated with higher tumor response rate at the expense of increased toxicity. Although triplet therapy had a better overall survival compared to doublet therapy, this did not reach statistical significance. [Copyright &y& Elsevier]

Abstract: Although results of autologous stem cell transplantation (SCT) for recurrent follicular non-Hodgkin lymphoma (NHL) have been previously reported, the long-term results and evaluation of prognostic factors in a large patient population receiving this therapy are difficult to find in the literature. To address these issues, we evaluated 248 patients with recurrent follicular NHL treated with high-dose chemotherapy and autologous SCT between 7/87 and 6/03. According to the World Health Organization (WHO) classification system, 64 patients (26%) had follicular NHL grade 1 (FL 1), 98 (40%) had FL 2, and 86 (35%) had FL 3. At the time of transplantation, 88 of the patients (35%) had a Follicular Lymphoma International Prognostic Index (FLIPI) score of low risk, 87 (35%) had an intermediate-risk FLIPI score, 37 (15%) had a high-risk FLIPI score, and 36 (15%) had at least 1 missing value, preventing calculation of the FLIPI score. The 5-year overall survival (OS) for all patients was 63%, and the 5-year progression-free survival (PFS) was 44%. In a multivariate analysis, a histological grade of FL 3, a high-risk FLIPI score at the time of transplantation, and having received 3 or more previous chemotherapy regimens were significant factors for predicting a worse OS. In addition, the use of a transplantation regimen including a monoclonal antibody decreased the relative risk of progressive lymphoma. These data suggest that transplantation earlier in the course of the disease for patients with follicular lymphoma with use of a monoclonal antibody–based regimen may lead to improved outcomes. [Copyright &y& Elsevier]

• VOD/SOS incidence at 100 days post-HCT was 4% versus 3% in GO-exposed adults versus control subjects. • Five-year overall survival probability was 38% in both groups. • GO exposure before HCT was not associated with an increased risk of VOD/SOS or death. Gemtuzumab ozogamicin (GO) therapy before allogeneic hematopoietic cell transplantation (alloHCT) has been historically associated with an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in patients with acute myeloid leukemia (AML). The current analysis examined VOD/SOS risk and outcomes in a cohort of patients who in recent years were reported to the Center for International Blood and Marrow Transplant Research. Adults with AML who had GO exposure before myeloablative alloHCT were matched 1:4 by age and disease status at transplant to recipients without GO exposure (control subjects). One hundred thirty-seven patients with GO exposure and 548 matched control subjects who underwent alloHCT between 2008 and 2011 were included in this analysis. With a median ∼8-year follow-up of survivors, the 5-year overall survival probability was similar in the 2 cohorts: 38% and 38% in the GO-exposed versus control groups (P =.97). Incidence of VOD/SOS and severe VOD/SOS, respectively, at 100 days was 4% (95% confidence interval [CI], 1% to 7%) and 3% (95% CI, 1% to 6%) in GO-exposed patients and 3% (95% CI, 2% to 5%) and 1% (95% CI, 0% to 2%) in control subjects. Correspondingly, among patients who developed VOD/SOS, 1-year survival probability after VOD/SOS diagnosis was 33% (95% CI, 5% to 72%) and 27% (95% CI, 11% to 47%; P =.78). In multivariate analyses, GO exposure before alloHCT was not associated with an increased risk of VOD/SOS (odds ratio, 1.10; P =.85) or death (hazard ratio, 1.08; P =.57). Three deaths (3%) in the GO group and 3 deaths (<1%) in the control group were attributed to VOD/SOS. Our results suggest that GO treatment before myeloablative alloHCT in the recent era is not associated with an increased risk of post-transplant VOD/SOS or death. [ABSTRACT FROM AUTHOR]

Abstract: To compare the clinical outcomes of older (age ≥55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged ≥55 years to 1949 NHL patients <55 years during the years 1990–2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended. [Copyright &y& Elsevier]

Hematopoietic cell transplantation is an elective procedure that results in prolonged immune suppression and high treatment-related morbidity and mortality. Transplant centers and physicians use a variety of prophylaxis and monitoring strategies to prevent or minimize complications. Little is known about the variability in these practices. We conducted an international Internet-based survey of 526 physicians to describe the spectrum of supportive care practices employed. Consistency in pretransplant cardiac (96%) and pulmonary (95%) screening, informed consent documentation (93%), and use of antifungal prophylaxis (92%) was observed. Greater heterogeneity was seen in use of myelogenous growth factors, empiric antibiotic therapy, protective isolation procedures, posttransplant monitoring, and environmental and social restrictions. Although some practice differences were associated with physician characteristics and transplant type, most practice variation remained unexplained. These results suggest a need for well-designed observational and interventional studies to provide data about which supportive care practices improve outcomes. For practices proved to be beneficial, publication of guidelines and incorporation of monitoring into quality improvement initiatives may help standardize practices. [Copyright &y& Elsevier]

We evaluated whether or not a patient''s area of primary residence is an independent risk factor for overall survival (OS) after HLA-identical sibling or autologous hematopoietic stem cell transplantation (HSCT). This retrospective cohort study included patients who underwent autologous (n = 1739) or HLA-identical sibling (n = 267) HSCT to treat a hematologic malignancy between 1983 and 2004 at the University of Nebraska Medical Center. Primary area of residence, using the patient''s zip code, was categorized as either urban or rural (including isolated, small rural, or large rural) according to the Rural Urban Commuting Area Codes (RUCA) classification system. An association between area of primary residence and survival was examined using Cox proportional hazards regression analysis while adjusting for patient-, disease-, and treatment-related variables. Patients from rural areas who received autologous HSCT had a higher relative risk of death (relative risk = 1.18; P = .016) than urban patients who underwent the same procedure. Survival rates in patients from rural and urban locations are as follows: 1 year, 73% vs 78% (P = .04); 5 year, 48% vs 54% (P = .012). We failed to detect a significant difference in the risk of death according to primary area of residence in the HLA-identical sibling HSCT cohort, although this may be from lack of statistical power. Our findings suggest that the primary location of a patient''s residence may be an independent risk factor for survival after HSCT. [Copyright &y& Elsevier]