5005 Chronic myelogenous leukemia (CML) and multiple myeloma (MM) are hematological neoplasms with involvement of distinct hematopoietic cell lineages. The simultaneous occurrence of CML and MM is an extremely rare event. We report the case of a 46-year-old asymptomatic patient who was diagnosed with CML after an abnormal white blood cell count (90×109 u/L) was found on a routine complete blood cell count. Physical examination showed only splenomegaly. At diagnosis, a monoclonal protein peak was observed on electrophoresis (0.82g/dL). Bone marrow (BM) biopsy was characterized by granulocyte hyperplasia without clonal plasmacytosis. Karyotype showed t(9;22)(q34.1;q11.2) and a BCR/ABL mRNA transcript was detected by RT-PCR. Cytoreduction was initiated with hydroxyurea for 20 days until imatinib 400 mg/day was initiated. Patient achieved a major molecular response (MMR) after 7 months of treatment and remains in MMR. After 12 months from diagnosis, the patient persisted with monoclonal peak, and a new BM biopsy showed 15% monoclonal plasma cells, compatible with IgG lambda Myeloma. No end-organ damage was found, and there was no indication for therapy. Karyotype was 46, XX and a FISH analysis was positive for IgH rearrangement and for del 13q. At the time of this report the patient persists in MMR for CML with a monoclonal peak of 1.2 g/dL. No evidence of MM progression has been observed. These findings indicate coexistence of CML in chronic phase and monoclonal gamopathy of uncertain significance (MGUS), progressing to smoldering MM IgG lambda during IM treatment. At this moment, the association of CML and MM has been considered coincidental, but it is possible that imatinib may induce changes in phenotype of plasma cells which might lead to progression of multiple myeloma. Disclosures: No relevant conflicts of interest to declare.
4208 Introduction: Despite preventive and therapeutic antiviral medication cytomegalovirus (CMV) infection is still a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT). Only limited data on CMV infection and disease are available in autologous SCT recipients. Previous studies have demonstrated that the probability of CMV infection is nearly 60% in seropositive patients and 23% in seronegative patients undergoing autologous SCT, but its impact in mortality is unclear. Methods: We retrospectively reviewed the medical records of 101 patients undergoing autologous SCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. CMV infection was defined as a quantitative real time PCR assay showing greater than 165 copies and/or positive CMV pp65 antigenemia assay. Lymphocyte count was registered at 15th day after SCT and lymphopenia was defined as an absolute lymphocytes count (ALC) < 500 at that time point. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. CMV infection was analyzed as a time-dependent covariate, considering the time to CMV infection. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: The majority of patients were male (62.4%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (92%). A positive serological CMV status was found in 93.75% of patients. Most common indications for autologous SCT were multiple myeloma (34%), non-Hodgkin's lymphoma (40%) and Hodgkin's lymphoma (6%). After a median follow-up of 2 years, the OS for the whole cohort was 61% (95% confidence interval [CI] 48–72%). CMV infection post SCT was seen in 26% of patients. In the univariate analysis, development of CMV infection and presence of D15 lymphopenia were associated with a higher mortality (CMV infection-hazard ratio [HR] 3.32 [95%IC 1.61–6.84]; p= 0.001; D15 lymphopenia- HR 2.37 [95% IC 1.11–5.05]; p= 0.024). Patients who developed CMV infection in the setting of D15 lymphopenia had the worse outcome (2-years OS 19%; 95% CI 9–43%; figure 1). D15 lymphopenia was not associated with a higher rates of CMV infection (p=0.41). In Cox multivariate analysis, lower overall survival was demonstrated in female patients (HR= 2.23, 95%IC 1.08–4.58; p= 0.029), in the presence of D15 lymphopenia (HR= 2.56, 95%IC 1.19–5.51; p= 0.016) and CMV infection (HR: 3.33, 95% IC1.61–46.86; p= 0.001). Conclusion: CMV infection post-autologous SCT is associated with a decreased survival, and in the concomitant presence of D15 lymphopenia appears to indicate a subgroup of patients with very poor outcome. It is possible that CMV infection does not lead directly to increased mortality, but is rather a surrogate marker of decreased immune function post-ASCT. Future studies should prospectively evaluate the incidence and prognostic impact of CMV infection post-ASCT and correlate with markers of immune recovery. Disclosures: No relevant conflicts of interest to declare.
4540 Introduction: Several studies have suggested that the peripheral blood absolute lymphocyte count (ALC) at arbitrary time points after ASCT is associated with improved survival and decreased relapse rate. Most reports have focused on one type of hematological malignancy, and different time points (i.e. day 15, day 21) and ALC values (> 0.35×109/L, > 0.5×109/L) have been studied. We hypothesized that the immune recovery post ASCT is an important predictor of long term outcome independent of disease, and that more important than the value of ALC at a specific time point, is the time to lymphocyte recovery post-ASCT. Methods: The medical records of patients that underwent ASCT at our institution from January 2005 until May 2010 were reviewed and information on ALC count at day 15 and time to lymphocyte recovery was retrieved. Lymphocyte recovery was defined as the first of at least two consecutive days with > 0.5×109/L lymphocytes on the peripheral blood. Overall survival was defined as time from ASCT until death from any cause. OS was estimated by Kaplan-Meier and compared by logrank. Cox proportional hazards models was used to determine covariates associated with OS in a multivariate analysis. Variables were entered and selected in a backwards fashion with a p cutoff of 0.05. Results: Ninety-two patients were analyzed. Diagnosis included: multiple myeloma (N=35), non-Hodgkin's lymphoma (N=33), solid tumors (N=8), Hodgkin's lymphoma (N=8), acute myeloid leukemia (N=4), amyloidosis AL (N=3) and chronic myeloid leukemia (N=1). Median age was 55 years (range 3–74 years). OS at 2 years for the entire cohort was 51% (95% CI 37–66%). There were 47 patients (51%) with an ALC at day 15 (ALC-15) ≥ 0.5×109/L, and these patients had a significantly superior OS compared to patients with an ALC-15 < 0.5×109/L (2-years OS: 68% vs. 35%, p=0.01). Median time to lymphocyte recovery was 15 days (range 8–314 days). Patients with a rapid (≤ 15 days) lymphocyte recovery had superior OS compared to those with a slower (> 15 days) lymphocyte recovery (2-years OS: 66% vs. 31%, p=0.002). Median OS for those with a quick recovery was not reached, while for patients with a slow recovery was 16 months (95% CI 3–29 months). In a Cox proportional hazards analysis, the following variables were added: age, diagnosis of multiple myeloma (yes vs. no), ALC-15 < 0.5×109/L (yes vs. no) and slow lymphocyte recovery (yes vs. no). Only diagnosis of multiple myeloma (hazard ratio [HR] 0.25 [95% CI 0.09–0.67], p=0.006) and slow lymphocyte recovery (HR 3.18, [95% CI 1.44–7.03], p=0.004) were associated with OS, while ALC-15 was not. Conclusion: Our results suggest that the kinetics of lymphocyte recovery have an important impact on survival post-ASCT. Our findings need to be confirmed in other cohorts. Strategies to modulate immune function post-ASCT should be the subject of future studies. Disclosures: No relevant conflicts of interest to declare.
4531 Introduction: Cytomegalovirus (CMV) is one of the most common viral pathogens post-allogeneic stem cell transplantation (SCT). However, CMV reactivation and disease are relatively uncommon events after autologous stem cell transplantation (ASCT), with a reported incidence of 2–9%. There are few studies describing risk factors for development of CMV reactivation post-ASCT. Objective: To describe the incidence and risk factors for CMV reactivation post-ASCT in our institution and its impact on survival. Methods: The charts of patients who underwent ASCT at our institution from January 2005 until July 2009 were manually reviewed. CMV reactivation was detected by antigenemia assay and/or real-time PCR. Variables associated with CMV in a univariate analysis with a p<0.15 were included into a multivariable logistic regression model to determine risk factors for developing CMV reactivation. Overall survival (OS) was defined from time of ASCT until death from any cause and was estimated by Kaplan-Meier method. Logrank test was used to compare unadjusted OS between patients with and without CMV reactivation. Results: A total of 115 ASCTs were performed at our institution during that time frame (bone marrow=8; peripheral blood stem cells=107). CMV reactivation was investigated in 50 patients (43.5%) who presented with persistent fever and 14 (12.3%) were found to be positive for CMV by either antigenemia and/or real-time PCR. Diagnosis included multiple myeloma (N=7) non-Hodgkin's lymphoma (N=6) and multiple sclerosis (N=1). Median time to CMV reactivation was 18 days (range 12–41). Seventy-two patients had information on absolute lymphocyte count at day 15. Patients with an ALC < 0.5×109/L at day 15 had a higher incidence of CMV reactivation (28.5% vs. 8%, p=0.02). Variables entered in the logistic regression multivariate analysis were age, sex, years between diagnosis and ASCT and ASCT in the last 12 months. Only age (odds ratio [OR]=1.06; p=0.05) and ASCT in the last year (OR=3.7; p=0.03) were significantly associated with CMV reactivation in the multivariate analysis. When analyzing only the 72 patients that had information on day 15 ALC, the multivariate analysis revealed ASCT in the last 12 months (OR=1.56, p=0.05) and day 15 ALC < 0.5×109/L (OR=4.71, p=0.03) as being associated with CMV reactivation. Patients who had CMV reactivation had a significantly inferior OS (2-years 61% vs. 23.4%, p=0.03). Conclusion: We detected a relatively high incidence of CMV infection post-ASCT and this was associated with a higher mortality. Patients who develop CMV infection post-ASCT may represent a subset that has a higher degree of immunesuppression, as manifested by a lower ALC at day 15 post ASCT. We believe that patients should be monitored post-ASCT for the presence of CMV reactivation, particularly if they present with persistent lymphopenia. Disclosures: No relevant conflicts of interest to declare.
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