ABSTRACT
High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains a valuable therapeutic approach for relapsed and refractory (R/R) patients with diffuse large B-cell lymphoma (DLBCL). The aim of the study was to evaluate the safety and clinical outcome of ASCT for R/R DLBCL. We present a retrospective series of ASCT for 53 DLBCL patients (30 males and 23 females) at the median age of 51 years. Patients were eligible for transplantation if they achieved partial, second, or subsequent response or remained stable to at least 2 prior treatments. Median overall (OS) and progression-free (PFS) survivals were 9 and 6.3 years, respectively. The estimated 4-year OS and PFS were found to be 75% and 69%, respectively. In univariate analysis liver involvement, clinical stage at diagnosis, lymphocyte/monocyte count, and status of clinical response at ASCT were found to influence OS, however, only absolute lymphocyte count remained significant in multivariate analysis (HR 1.42 [95% CI: 1.08-1.87]; p=0.01). Median follow-up from ASCT to the last contact was 4.4 years (range 0.03-18.7). In total, 26 patients died from disease progression and subsequent resistance to chemotherapy. At the last contact, 27 patients were alive in remission. Only a single patient died shortly after ASCT due to infectious complications. Grade 3 or 4 non-hematological side effects were not observed in the remaining patients. ASCT for RR DLBCL is a safe procedure with a high probability of overall and progression-free survival.
Subject(s)
Drug Resistance, Neoplasm , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/therapy , Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Transplantation, AutologousABSTRACT
The incorporation of pegylated asparaginase (PEG-ASP) in pediatric and adult acute lymphoblastic leukemia (ALL) protocols remains a worldwide therapeutic approach. However the safety profile remains a challenge, and herein we report the toxicity of an intravenous single dose of 1000 IU/m2 PEG-ASP administered in remission induction for adult ALL patients. Thirty-two patients at median diagnostic age of 32 years (median of 19-65) were included in this analysis. Most patients had B-cell lymphoblastic leukemia (n=26; 78%) and 81% of cases were <55 years at study entry. 75% of patients had <30x109/l leukocyte count at diagnosis and median follow-up was 14 months (range 0.8-69). All grade 3/4 adverse events (AEs) after PEG-ASP administration were observed in 24 patients (75%). The most common grade 3/4 AEs were: decreased fibrinogen (58%), increased bilirubin (31%) and increased GGTP (27%). Clinical manifestations related to PEG-ASP were seen in 9 patients and included: abdominal pain (n=6), thrombosis (n=2), diarrhea (n=1) and pancreatitis (n=1). The median time from PEG-ASP administration to first toxic symptoms was 7 days (range 1-19), and there were also 4 (13%) early induction deaths. All deaths were observed in ≥50-year-old patients after a median of 5 days following PEG-ASP (range 1-9). Three of these four patients had massive obesity. While all expired patients had grade 4 neutropenia and thrombocytopenia at the time of death, sepsis was not present. Administration of PEG-ASP in induction remission for ALL patients resulted in a significant, but mostly reversible hepatotoxicity. This PEG-ASP treatment should be administered with caution for older, obese patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Asparaginase/therapeutic use , Polyethylene Glycols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Humans , Middle Aged , Remission Induction , Young AdultABSTRACT
The studies material comprised 10 placentae from pregnancies at risk for premature labour with delayed intrauterine growth of the fetus treated with Salbupart from the 32nd week of pregnancy. In placental homogenates the biochemical components were determined for fragmentary assessment of carbohydrate and lipid metabolism and production on high-energy compounds. Salbupart was found to increase the oxidation processes in the placenta. This increases the production of biologically useful chemical energy which is expressed as increased energy charge (so called Atkinson's index or adenylate energy charge). Increased energy yield of the placenta results in improved materno-fetal transport and contributes to greater weight gain of the hypotrophic fetus.
