Autologous Stem Cell Transplant Recipients Research Articles

Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research

The optimal post-remission treatment for acute myeloid leukemia in first complete remission remains uncertain. Previous comparisons of autologous versus allogeneic hematopoietic cell transplantation noted higher relapse, but lower treatment-related mortality though using bone marrow grafts, with treatment-related mortality of 12-20%. Recognizing lower treatment-related mortality using autologous peripheral blood grafts, in an analysis of registry data from the Center for International Blood and Transplant Research, we compared treatment-related mortality, relapse, leukemia-free survival, and overall survival for patients with acute myeloid leukemia in first complete remission (median ages 36-44, range 19-60) receiving myeloablative HLA-matched sibling donor grafts (bone marrow, n=475 or peripheral blood, n=428) versus autologous peripheral blood (n=230). The 5-year cumulative incidence of treatment-related mortality was 19% (95% confidence interval, 16-23%), 20% (17-24%) and 8% (5-12%) for allogeneic bone marrow, allogeneic peripheral blood and autologous peripheral blood stem cell transplant recipients, respectively. The corresponding figures for 5-year cumulative incidence of relapse were 20% (17-24%), 26% (21-30%) and 45% (38-52%), respectively. At 5 years, leukemia-free survival and overall survival rates were similar: allogeneic bone marrow 61% (56-65%) and 64% (59-68%); allogeneic peripheral blood 54% (49-59%) and 59% (54-64%); autologous peripheral blood 47% (40-54%) and 54% (47-60%); P=0.13 and P=0.19, respectively. In multivariate analysis the incidence of treatment-related mortality was lower after autologous peripheral blood transplantation than after allogeneic bone marrow/peripheral blood transplants [relative risk 0.37 (0.20-0.69); P=0.001], but treatment failure (death or relapse) after autologous peripheral blood was significantly more likely [relative risk 1.32 (1.06-1.64); P=0.011]. The 5-year overall survival, however, was similar in patients who received autologous peripheral blood (n=230) [relative risk 1.23 (0.98-1.55); P=0.071] or allogeneic bone marrow/peripheral blood (n=903). In the absence of an HLA-matched sibling donor, autologous peripheral blood may provide acceptable alternative post-remission therapy for patients with acute myeloid leukemia in first complete remission.

Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation

A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28-month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette-Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT-GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT-GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT-GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] -0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI -0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT-GIT outcomes was 2.80 per 100 person-years (95% CI 0.07-15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person-years (95% CI 0-8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT-GIT test was poor, regardless of BCG vaccination history.

Active cytomegalovirus infection in autologous stem cell transplant recipients: Incidence and clinical impact

Cytomegalovirus (CMV) infection in patients after autologous stem cell transplant (ASCT) has become a major medical concern. However, few studies have reported active CMV infection before the transplantation. In this study, we retrospectively analyzed the incidence, clinical impact, risk factors, and outcome of CMV pp65 antigenemia in 44 consecutive patients who underwent ASCT between January 2005 and June 2011. CMV pp65 antigenemia assay was performed weekly, from 7 days before stem cell infusion until the patient was discharged. All patients were CMV seropositive before ASCT. Pre-transplantation antigenemia was detected in 19 patients (43.2%) and post-transplantation antigenemia in 17 patients (38.6%). Multivariate analysis could not identify any pre-transplantation risk factors for CMV antigenemia. When patients with and without pre-transplantation antigenemia were compared, we found that pre-transplantation active CMV infection had significant effects on post-transplantation platelet and neutrophil recovery, although the time of hospitalization and amount of blood transfusion were similar in both groups. CMV antigenemia was asymptomatic in all cases, and cleared spontaneously in 86.7% of patients who did not receive antiviral treatment. In conclusion, CMV reactivation before ASCT might occur frequently and even an asymptomatic infection could significantly delay engraftment. Therefore, ASCT candidates should be routinely evaluated for active CMV infection. Key words: Cytomegalovirus, autologous stem cell transplant, CMV pp65 antigenemia, infection

Comparison of Clostridium Difficile Associated Diarrhea Detection by Enzyme Linked Immunosorbent Assay (EIA) and Polymerase Chain Reaction (PCR) in Autologous Hematopoietic Stem Cell Transplant (AHSCT) Recipients

Abstract 4739 Background:Diarrhea is a frequent complication of autologous hematopoietic stem cell transplantation and is a common cause of morbidity. Clostridium difficile associated diarrhea (CDAD) is the most common cause of nosocomial infections. Detection of CDAD is widely performed using enzyme linked immunosorbent assay (EIA) to C. difficile toxins A and B because of its technical ease of use and rapid results. The sensitivity of EIA is 60%, but the sensitivity increases with repeated testing. Recently, detection of CDAD by Polymerase Chain Reaction (PCR) methodology has resulted in rapid detection of amplified C. difficile toxin (CDT) B chromosomal material and has been shown to be more sensitive than EIA in patients suspected of CDAD; however, no comparison of the two methodologies has been performed in recipients of an autologous hematopoietic AHSCT. Methods:This retrospective analysis of AHSCT recipients at our institution evaluates the incidence of CDAD when using either EIA or PCR. CDAD was assessed at the onset of diarrhea in both cohorts. The time period of interest was from 7 days prior to transplantation to 30 days posttransplanation. In the EIA cohort, three consecutive liquid stools were tested for the presence of CDT A and B by EIA. In the PCR cohort, only one liquid stool was sent for sampling. Our institution adopted PCR methodology on 1 February 2010. Demographic and clinical information were collected to assess CDAD risk. Successful treatment of CDAD was defined as resolution of diarrhea within seven days. Previously published data from our institution have shown the incidence of CDAD to be 15% when using EIA methodology. Nominal data were analyzed by Fisher's Exact Test and continuous data were analyzed by Student's T-Test. Results:A total of 159 patients were screened; and 16 patients were excluded because they did not have a CDAD test performed. Seventy-three were included in the EIA cohort and 69 were included in the PCR cohort. Clinical characteristics were similar between the groups. Known risk factors for CDAD including days in the hospital, days of neutropenia, and days of prophylactic and intravenous antibiotics used were similar between the cohorts. The incidence of a positive CDAD test was higher in the EIA cohort compared to the PCR cohort (18% vs. 7% [p = 0.049]). The duration of diarrhea was longer in the EIA cohort as compared to the PCR cohort (7.3 days vs. 5.5 days [0.016]). Of the three consecutive EIA tests sent, the first was positive only 30% (4/13) of the time. Metronidazole was the first-line agent used in all cases. Response to therapy was poor in both the EIA and PCR cohorts with rates of 30% and 20%, respectively. No fatalities occurred in either group as a result of CDAD. Conclusion:The incidence of diarrhea was significantly shorter in the PCR cohort as compared to the EIA cohort. The duration of diarrhea was significantly shorter in the PCR group as compared to the EIA cohort. It is possible that repeated testing for CDAD by EIA decreases the specificity of the test or that the EIA is detecting a non-toxigenic C. difficile enterotoxin. Because our patient population has additional causes of diarrhea including mucosal irritation caused by chemotherapy, additional studies are needed to discern the discrepancies between both methodologies.EIA Cohort (n=73)PCR Cohort (n=69)P valueAge (median, years)61600.163Race (n,%)36 (49)38 (55)0.521Caucasion19 (26)20 (29)African American17 (23)11 (16)Hispanic1 (1)0 (0)OtherMale (n,%)71 (97)64 (93)0.265Karnofsky Performance Status (median,%)90900.932Disease (n,%)56 (77)45 (65)0.625Myeloma15 (20)21 (30)Lymphoma2 (3)3 (5)OtherCDAD (n,%)13 (18)5 (7)0.049Diarrhea Duration (mean, days)7.35.50.016 (−3.32 to −0.16)CDAD treatment response (n,%)4 (30)1 (20)0.568Days of Neutropenia (mean, days)76.70.553 (−1.01 to 0.54)Days of oral antibiotics (mean, days)4.54.30.774 (−1.04 to 0.77)Days of IV antibiotics (mean, days)7.35.50.170 (−4.33 to 0.77) Disclosures:No relevant conflicts of interest to declare.

Evidence of simian virus 40 infection in multiple organ transplant recipients with renal dysfunction

Electron microscopy (EM), real-time polymerase chain reaction (PCR) and conventional PCR were used to identify viruses associated with infection in 2 transplantation patients. An autologous haematopoietic stem cell, liver and renal transplant recipient was found to be positive for simian virus 40 (SV40). Dual BK virus and SV40 infection was found in a heart and renal transplantation patient. SV40 infection can occur in immunocompromised patients.

Serum cortisol and inflammatory response in neutropenic fever

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8-9 a.m. on days 1-4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated.

The Cost of Herpes Zoster Among Autologous Hematopoietic Stem Cell Transplant Recipients

The Cost of Herpes Zoster Among Autologous Hematopoietic Stem Cell Transplant Recipients

The humoral immune response of hematopoietic stem cell transplantation recipients to AS03-adjuvanted A/California/7/2009 (H1N1)v-like virus vaccine during the 2009 pandemic

We evaluated the formation of hemagglutination-inhibition (HI) antibodies in response to vaccination of 55 allogeneic and 23 autologous hematopoietic stem cell transplantation (HSCT) recipients with 3.75 μg inactivated influenza A/California/7/2009 (H1N1)v-like virus adjuvanted with AS03, given towards the end of the 2009 influenza pandemic. The 78 HSCT recipients, aged 11–72 (median 50) years, were vaccinated 1–290 (median 27) months post-HSCT. Of the 55 allogeneic HSCT recipients, 50.9% received reduced intensity conditioning, 74.5% had a sibling donor, 67.2% had active graft-versus-host disease and 43.6% were on steroid therapy. At baseline, 14/78 (17.9%) had HI titers ≥1:40. Blood samples of 77 patients were available post-1st vaccination; of these, 34 (44.2%) patients had HI titers ≥1:40. Blood samples of 43 patients were available post-2nd vaccination; of these, 21 (48.8%) had HI titers ≥1:40. There was a significant increase in HI titers ≥1:40 from baseline to both post-1st and 2nd vaccinations ( p < 0.001 each), and also from 1st to 2nd vaccination ( p = 0.008). In seronegative (HI titers <1:10) patients, whose sera were available before, after one dose, and after 2 doses of vaccine, seroconversion (to ≥1:40) occurred in 4/24 (16.7%) after 1-dose and in a total of 10/24 (41.7%) after 2-dose vaccination ( p = 0.031). Logistic regression analysis revealed that ≥1:40 HI titers were significantly associated with higher lymphocyte counts and higher HI baseline titers and, in allogeneic HSCT, with having a sibling donor and higher baseline titers. In conclusion, 2-dose vaccination with AS03-adjuvanted vaccine containing 3.75 μg antigen resulted in a statistically significant, yet limited, serological response. Therefore, additional precautions should be taken during influenza outbreaks.

Secondary malignancies after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) offers patients with malignant and nonmalignant diseases the oportunity to pursue life-prolonging therapy. The number of survivors after successful HSCT is continually increasing. However, HSCT can induce tissue and organ damage that occurs not only "on treatment" , but long after completing therapy. Secondary malignancies belong to serious late complications after HSCT. A significant association of certain risk factors with increased likelihood of secondary malignancies after HSCT has been published over the last ten years. Better knowledge of pathogenesis of these complications, their early identification and treatment may contribute to better health outcomes of allogeneic and autologous hematopoietic stem cell transplantation recipients. We review here the incidence and risk factors of secondary malignancies after hematopoietic stem cell transplantation.

Long-Term Surveillance of Allogeneic and Autologous Hemopoietic Stem Cell Transplant Recipients Affected by Primary Occult Hepatitis B Virus Infection

AbstractAbstract 3350 Introduction:In the absence of serum hepatitis B (HB) surface antigen (HBsAg) and clinical evidence of HB, an occult HB virus (HBV) infection (OBI) is defined as the existence of HBV DNA in the serum, in the peripheral blood mononuclear cells (PBMC), and/or in the liver. Most frequently, OBI follows the resolution of acute hepatitis and continues indefinitely after HBsAg clearance and liver function improvement. Usually, this form of infection, termed secondary OBI (sOBI), is associated with the presence of serum anti-HB core antibodies (anti-HBc). Up to 20% of individuals with OBI do not react for either anti-HBc or any other serological indicator of HBV exposure. Consistent with the woodchuck model, this form of infection, termed primary OBI (pOBI), is characterized by the presence of DNA in both serum and PBMC, but not in the liver. Although reactivation of sOBI has been reported in a high proportion of hemopoietic stem cell transplant (HSCT) recipients, pOBI reactivation risk has not yet been fully investigated in the transplant setting. We followed up 9 long term surviving HSCT recipients with pOBI, in order to define its clinical significance in immune suppressed patients. Patients and Methods:A total of 75 consecutive patients with hematological disease, receiving autologous or allogeneic HSCT between April 2006 and March 2007, were included in a database and retrospectively examined. As a prerequisite for inclusion in the study, each of the following was needed: (i) negative serological indicators of HBV exposure and absence of clinical signs/symptoms of hepatitis at the time of HSCT, (ii) positive HBV DNA, as detected by polymerase chain reaction (PCR), in both serum and PBMC samples drawn within 6 months before transplant, and (iii) availability of stocked frozen serum/PBMC samples collected after HSCT from each patient. Following these criteria, 9 patients (7 males, 2 females) were selected for the analysis. Five patients (1 Hodgkin disease, 3 non-Hodgkin lymphomas, and 1 B-cell chronic lymphocytic leukemia) received autologous HSCT, and 4 patients (1 acute myeloid leukemia, 1 multiple myeloma, 1 myelodysplastic syndrome, and 1 acute lymphoblastic leukemia) received allogeneic HSCT. Median age at transplant was 49 (range: 33–63) years. No patient received lamivudine prophylaxis. Serum and PBMC samples collected after HSCT were analyzed for HBV serology and DNA detection. The latter was performed by in-house PCR amplification by nested primers (detection limit 50 copies/ml) from highly conserved S region encompassing a-determinant of HBV. Direct sequencing of all HBV DNA amplified products was used to confirm the specificity of the reaction. Results:In 8 cases, one serum/PBMC sample per patient was available, at a median of 27 (range: 21–34) months after HSCT; in 1 case, three serum/PBMC samples were available, at 17, 22, and 28 months after HSCT, respectively. During follow-up, positive HBV DNA was found, both in the serum and in the PBMC. All patients were confirmed to be infected with HBV subgenotype D1, with mutations known to impair HBsAg antigenicity. Three patients were confirmed to be further infected with HBV subgenotype A2. So far, 41 to 52 months after transplant (median: 46 months), neither patients showed seroconversion nor developed clinical hepatitis, suggesting pOBI persistence. Conclusions:Although the virus persisting in pOBI remains biologically competent, it is likely neither to reach liver-pathogenic doses nor to induce “classical” HBV reactivation during PBMC-restricted replication. However, prospective studies with large sample size and long-term follow-up are warranted, to define the actual clinical relevance of HBV occult infection. Indeed, OBI with low viremia could induce DNA damage, cellular demise, immune hypo-responsiveness, and oxidative stress in peripheral blood lymphocytes. Disclosures:No relevant conflicts of interest to declare.

Pancytopenia and myeloid maturation arrest in an autologous stem cell transplant recipient

Pancytopenia and myeloid maturation arrest in an autologous stem cell transplant recipient

Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients. None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positive for HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs- and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05). Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.

Erythropoietin-Assisted Phlebotomy in Stem Cell Transplant Patients with Iron Overload.

Abstract 4296▪ BackgroundStem cell transplantation is a potential curative treatment for hematologic malignancies. This treatment often requires repeated packed red blood cell (PRBC) transfusion requirements raising the risk of secondary hemochromatosis with each successive unit transfused. Erythropoietin-assisted phlebotomy is a potential treatment to alleviate iron overload in transfusion-dependent patients. MethodsWe carried out a retrospective review from 2000 to 2008 of records of both allogeneic and autologous stem cell transplant recipients treated at San Antonio Military Medical Center South for a total of 372 patients. We evaluated the maximum level of ferritin recorded for each patient and used an upper level of 1,000 ug/mL (approx 2.5x upper level of normal) to identify those patients at increased risk for complications of iron overload. 65 patients had ferritin levels <1,000ng/mL and served as a control group. There were 56 patients who met our criteria for iron overload. Their transfusion records were reviewed and further subdivided into those who received therapeutic erythropoietin-assisted phlebotomy and those who did not. They were also reviewed for evidence of any opportunistic infection during their treatment course. ResultsOf the 56 patients with documented ferritin levels over 1,000ug/mL, the average ferritin level was 2,965ug/mL. The transfusion records for these patients were obtained and showed that they received an average of 26.6 units of transfused PRBCs during their transplant course. Ten of these patients underwent therapeutic erythropoietin-assisted phlebotomy of 500cc of whole blood approximately once every two weeks to decrease their ferritin levels with a stated goal of <500ugmL. All records were then reviewed for evidence of opportunistic infections complicating treatment and corresponding mortality. The non-phlebotomized group had an increased rate of infections and trended toward a higher mortality rate. Overall infections were significantly different, with the hyperferritinemia group who did not receive phlebotomy having the highest rates within our three groups at both the three and six month intervals (p<0.004 and p<0.008). These differences were not significant at one year (p<0.086). When we compared the two main groups (ferritin <1,000 ng/ml and >1,000 ng/ml), infection rate results were higher in the hyperferritinemia group at all three time intervals (p<0.003, p<0.008 and p<0.049). There was no significant difference between infection rates in the erythropoietin-assisted-phlebotomy group and the control group at either the 3 or 6 month intervals. (p<0.17 and p<0.107) Mortality differences between the two main groups (ferritin >1,000ng/ml and ferritin <1,000 ng/ml) were significant at both six months and one year (p<0.0004 and p<0.005 respectively). There was also a significant difference noted between the hyperferritinemia group who did not receive phlebotomy and the ferritin <1,000 ng/ml group at both six months and one year (p<0.00002 and p<0.0004 respectively). Two-tailed Fishers exact test showed that the mortality rate between the two subsets in the hyperferritinemia group was significant at six months (p=0.009 two sided; p=0.005 one sided) but not at one year (p=0.34, two-sided; p=0.19 one sided). There was no significant difference in mortality rates between the erythropoietin-assisted-phlebotomy group and the control group. ConclusionsIron overload can be insidious. Multiple transfusions raise the risk for ferritin levels ≥1,000 ug/mL and predispose patients to secondary hemochromatosis which is a risk factor for opportunistic fungal and bacterial infections and may lead to increased mortality rates. Erythropoietin-assisted phlebotomy is a potential treatment to prevent the complications of iron overload in HSCT patients. Disclosures:No relevant conflicts of interest to declare.

High Oct-2 Protein Expression Is Associated with Decreased Overall Survival, While High Bob-1 Protein Expression Is Associated with Improved Overall Survival in Myeloma Patients.

Abstract 2822Poster Board II-798 Background:Oct-2 and Bob1 are B-lymphoid lineage specific transcription factors which drive the expression of genes involved in B-lymphocyte and plasma cell development and differentiation, including the immunoglobulin heavy chain (IgH) genes and many others. It is also thought that these transcription factors drive the overexpression of oncogenes involved in IgH translocations through upregulation of the IgH enhancers. We sought to evaluate the expression of Oct-2 and Bob1 in multiple myeloma, a malignancy of the B cell/plasmacyte lineage, in order to determine their potential biological significance as determinants of disease behaviour/prognosis and as potential therapeutic targets. Methods:A tissue microarray containing triplicate samples from 220 myeloma patient samples was generated. Samples were collected at the time of diagnosis between 1993 and 2008. To measure Oct-2 and Bob-1 protein expression in the CD138+ plasma cells of each sample, fluorescent immunohistochemistry was used to stain the samples and the HistoRx PM-2000 platformTM was used to generate an AQUA score for each patient. Oct-2 AQUA scores were available for 169 patient samples and Bob-1 AQUA scores were available for 169 patient samples. The analysis was repeated using conventional immunohistochemistry and visual scoring of staining intensity. Results:The Oct-2 and Bob-1 AQUA scores were continuously distributed over the patient cohort; thus, subsequent analyses were done by dividing the patient cohort by the median Oct-2 or Bob-1 AQUA score and comparing the group with high AQUA scores to the group with low AQUA scores. The patient group with high Oct-2 AQUA scores had an OS of 52.8 months compared to 73.1 months in the group with low Oct-2 AQUA scores (hazard ratio [HR]=1.74, 95% confidence interval [CI]=1.11-2.73, p=0.0164). The patient group with high Bob-1 AQUA scores had an OS of 70.5 months compared with 38.3 months in the group with low Bob-1 AQUA scores (HR=0.46, 95% CI=0.29-0.71, p=0.0008). In a Cox regression proportional hazards model including autologous stem cell transplant (ASCT) status, serum albumin, serum β2-microglobulin and Oct-2 or Bob-1 AQUA scores, only ASCT status was independently predictive of OS. The patient group with low Oct-2 AQUA scores had a significantly higher proportion of ASCT recipients than the group with high Oct-2 AQUA scores. Conversely, the patient group with high Bob-1 AQUA scores had a significantly higher proportion of ASCT recipients than the group with low Bob-1 AQUA scores. Results were similar but not statistically significant when analyzing the TMA with conventional immunohistochemistry and visual scoring of staining intensity. Discussion:In this retrospective study high Oct-2 expression was found to be associated with decreased OS, while high Bob-1 protein expression was associated with increased OS. These results suggest that Oct-2 is a negative prognostic factor in myeloma, while Bob-1 is a favorable prognostic factor, and demonstrates the applicability of the HistoRx platform to myeloma bone marrow TMA analysis. Since this was a small, exploratory study these results must be interpreted with caution and must be confirmed in a larger, prospective analysis. Disclosures:No relevant conflicts of interest to declare.

Immune reconstitution inflammatory syndrome associated withAspergillus terreuspulmonary infection in an autologous stem cell transplant recipient

We describe an autologous stem cell transplant recipient who developed immune reconstitution inflammatory syndrome (IRIS) associated with Aspergillus terreus invasive pulmonary infection after recovery from neutropenia. Clinical and radiological worsening of pulmonary invasive aspergillosis coincident with a robust decline of serum galactomannan values and rising neutrophil counts should be interpreted as IRIS and should not require changes to antifungal therapy.

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

Clinical Utility of Computed Tomography Screening of Chest, Abdomen, and Sinuses before Hematopoietic Stem Cell Transplantation: The St. Jude Experience

All allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) recipients at St. Jude Children's Research Hospital undergo pre-HSCT computed tomography (CT) of the sinuses, chest, and abdomen because they are at significant risk for opportunistic infections. We studied whether this extensive routine imaging is warranted to detect infection despite the risk of additional radiation exposure. We reviewed the medical records of all children receiving allo- and auto-HSCT at St. Jude in 2004 and 2005. Of the 184 eligible patients who received 187 transplants, 131 received allografts and 56 autografts. Solid tumors and lymphomas were removed from the final analysis of the chest and abdomen CT as this imaging is typically warranted as part of disease restaging; thus, 111 allogeneic participants were included in this analysis. Both auto- and allo-recipients were evaluated by sinus CT and included in this final analysis. Most allo- and auto-HSCT recipients (≥80%) did not have sinus, pulmonary, cardiac, or gastrointestinal symptoms; >85% of the evaluable allo-recipients had no prior fungal infection. Eighty-eight allo- and 31 auto-HSCT recipients had abnormal sinus CT findings, all unrelated to the underlying disease. Sixty-two (55.9%) of the allo-recipients had normal chest CT and 85 (76.6%) had normal abdominal CT. Of the 18 allo-recipients who began new therapy based on these findings, only 2 (11.1%) were related to chest CT findings and the other 16 were related to sinus findings. Our findings suggest that pre-HSCT routine CT imaging of the abdomen may not be warranted in a subset of allogeneic recipients who are asymptomatic and without previous infectious findings. Thus, these patients may be spared unnecessary radiation exposure. Recipients undergoing auto-HSCT or allo-HSCT for lymphomas or solid tumors will routinely undergo chest and abdominal CT imaging as part of their disease evaluation. The decision to perform chest CT should be made judiciously based on a careful history and physical examination. Sinus imaging, which was frequently abnormal, may be justified in all patients to plan post-HSCT care.

Imipenem/Cilastatin with or without Glycopeptide as Initial Antibiotic Therapy for Recipients of Autologous Stem Cell Transplantation: Results of a Spanish Multicenter Study

We analyzed the efficacy of imipenem/cilastatin alone (group I, 197 patients) or in combination with a glycopeptide (group I + G, 231 patients) as first-line antibiotic therapy for 2 consecutive cohorts of autologous stem cell transplantation (ASCT) recipients with febrile neutropenia. From June 2001 to June 2002, patients received imipenem/cilastatin (500 mg/6 hours), and from July 2002 to December 2003, they received imipenem/cilastatin as for group I plus a glycopeptide (vancomycin, 1 g/12 hours or teicoplanin, 400 mg/day). Fever of unknown origin accounted for 33.5% of episodes (66 patients) in group I and 50% of episodes (116 patients) in group I + G ( P = .005). Bacteremia occurred in 55 patients (28%) in group I and in 51 patients (22%) in group I + G ( P = .16). Resolution of fever without modification of the therapy regimen was observed in 108 patients (55%) and 159 patients (69%) in groups I and I + G, respectively ( P = .003). The median interval to defervescence (4 days) and overall mortality were similar between groups. Inclusion of a glycopeptide in the initial antibiotic regimen for febrile neutropenia results in a higher success rate without modifying the regimen. However, glycopeptide inclusion does not improve the interval to defervescence or mortality rate.

Spontaneous Autologous Acute Graft-Versus-Host Disease (GVHD) in Multiple Myeloma (MM) Autologous Stem Cell Transplant (ASCT) Recipients: A Surprisingly High Incidence

Spontaneous Autologous Acute Graft-Versus-Host Disease (GVHD) in Multiple Myeloma (MM) Autologous Stem Cell Transplant (ASCT) Recipients: A Surprisingly High Incidence

Severe sepsis in autologous stem cell transplant recipients: Microbiological aetiology, risk factors and outcome

Infectious complications are the main reason for early treatment-related mortality after autologous stem cell transplantation (ASCT). We evaluated retrospectively microbiological aetiology, risk factors and clinical consequences of severe sepsis in this patient cohort. From 1996 to 2006 a total of 319 patients underwent ASCT at our institution. Antibacterial prophylaxis was not used. Neutropenic fever occurred in 83% (n=265) and was complicated by severe sepsis in 5% (n=17) of patients. Severe sepsis tended to be more common in patients with non-Hodgkin's lymphoma (NHL) than in other patients (9% vs 3%, p=0.009). Bacteraemia was observed more commonly in patients with severe sepsis (76% vs 22%, p<0.001); Pseudomonas sp. was found in 30% (n=5) of these patients. Kinetics of C-reactive protein (CRP) more commonly coincided with, rather than predicted, the development of severe sepsis. All other observed risk factors for severe sepsis (length of neutropenia, fever and blood culture findings) were late indicators. Severe sepsis was fatal in 9 patients (53%), and all had NHL (p=0.003 compared to other patients). Severe sepsis is an important cause of early mortality after ASCT, especially in NHL patients. Ways to prevent development of severe sepsis or predict its development might reduce early mortality among ASCT recipients.