Utility of Comorbidity Assessment in Predicting Transplantation-Related Toxicity Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

AbstractPatients with coexisting medical problems may suffer increased toxicity and reduced quality of life after autologous hematopoietic stem cell transplantation (HSCT). The benefit of high-dose therapy for some patients with multiple myeloma (MM) is debatable. Decision tools that aid in identifying those patients with MM most suited for autologous HSCT may avoid the risk of excess toxicity. An objective assessment of comorbidities was performed in 126 patients with MM undergoing autologous HSCT using the Charlson comorbidity index (CCI), the hematopoietic cell transplantation comorbidity index (HCT-CI), and a modified pretransplantation assessment of mortality (mPAM) to determine the strength of association with increased transplantation-related toxicity and increased length of hospital stay (LOS). Any comorbidity scored using the CCI or HCT-CI (score > 0) was associated with an increased number of organ systems with serious toxicity (at least grade 2 toxicity using the Seattle criteria), an increased total sum of toxicity grades for all organs, and prolonged LOS. An mPAM score ≥ 24 was associated with increased LOS. When considering autologous HSCT for a patient with MM, assessment of comorbidities using the CCI or HCT-CI may assist in predicting the risk of transplantation-related toxicity as an adjunct to physician judgment and patient preference

A 15-Year Analysis of Early and Late Autologous Hematopoietic Stem Cell Transplant in Relapsed, Aggressive, Transformed, and Nontransformed Follicular Lymphoma

AbstractAutologous stem cell transplant (ASCT) has been shown to be an effective treatment for follicular lymphoma (FL). We explored our experience in ASCT for FL among all patients treated over a 15-year period from diagnosis through their entire treatment history including relapse post ASCT. All patients who underwent an unpurged ASCT for relapsed, advanced FL between June 1990 and December 2000 were analyzed. After salvage therapy they received melphalan/etoposide/total body irradiation, BCNU, etoposide, cytarabine, melphalan (BEAM), or cyclophosphamide BCNU etoposide (CBV) as conditioning for the ASCT. One hundred thirty-eight patients with a median age of 48 years and a median follow-up of 7.6 years were analyzed. The majority were of the subtype grade 1, nontransformed (FL-NT), having had 1 prior chemotherapy. The progression-free (PFS) and overall survival (OS) of the FL-NT at 10 years were 46% and 57%, respectively, and at 5 years for the transformed (FL-T) were 25% and 56%, respectively, of which only the PFS was significantly different (P = .007). The median OS from diagnosis was 16 years for the FL-NT. ASCT positively altered the trend of shorter remissions with subsequent chemotherapies, and there was no difference in OS between those who had 1, 2, or >2 chemotherapies prior to ASCT. Salvage therapy for relapse post ASCT was effective (OS >1 year) in a third of patients. Unpurged ASCT is an effective tool in the treatment of relapsed, aggressive FL-NT and FL-T, is superior to retreatment with standard chemotherapy, is effective at various stages of treatment, is likely to have a beneficial influence on the natural history of this disease, and the disease is amenable to salvage therapy post-ASCT relapse

Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

BACKGROUND: Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12+/-4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population. CONCLUSIONS/SIGNIFICANCE: Continuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis

Dead Space Ventilation Parallels Changes in Scintigraphic Vascular Obstruction at Recurrence of Pulmonary Embolism and after Thrombolytic Therapy: A Case Report

Physiological and alveolar dead space ventilation both increase in pulmonary embolism (PE) in proportion to the severity of vascular obstruction. The case of a patient with recurrent PE while on heparin therapy is presented. The recurrence was characterized clinically by severe pulmonary vascular obstruction and right heart dysfunction. The patient was treated with thrombolytic therapy, with excellent clinical and scintigraphic resolution. Dead space ventilation measurements at baseline, at the time of recurrence and after thrombolytic therapy are presented. The potential utility of dead space ventilation measurements for PE diagnosis and management are discussed