Recovery Of White Blood Cell Counts Research Articles

Association of Hospitalist Care and Outcomes for Patients Electively Admitted for Chemotherapy

Introduction: Patients with hematologic malignancies frequently receive elective anticancer therapy as inpatients. The impact of introducing hospitalists on quality outcomes in this subset of patients is unknown. Methods: Patients with leukemia or lymphoma electively admitted for anticancer therapy to either a hematologist-led service (TS; n=59) or to a hospitalist-led service (HS; n=102) during two parallel 18-month time periods were included. Mixed linear regression models with first-order random effects for intercept (individual) and slope (time) were used to estimate the association between service and the quality outcomes of length of stay (LOS), time from admission to anticancer therapy initiation, and discharge time of day. Results: For patients who received a fixed-duration anticancer therapy regimen, after adjustment for clinical and demographic covariates, mean LOS was reduced by >2 days (TS=5.97 days (95% CI: 5.13, 6.81); HS=3.88 days (95% CI, 3.53, 4.23); p<0.001), mean time from admission to first anticancer therapy administration decreased by 4 hours (TS=8.32 hours (95% CI: 5.72, 10.93); HS= 4.36 hours (95% CI: 3.49, 5.23); p=0.001)), and mean discharge time was similarly decreased by 110 minutes (TS=3:12 PM (95% CI: 2:06 PM, 4:19 PM); HS=1:22 PM (95% CI: 12:48 PM, 1:57 PM); p=0.01)). For regimens that required variable monitoring for post-treatment methotrexate clearance, tumor lysis syndrome, or white blood cell count recovery, no significant difference in outcomes was noted. Conclusion: Hospitalist care of patients with hematologic malignancies admitted for elective anticancer therapy may lead to improved quality and efficiency of care.

The Impact of 3S2E Nursing Management on the Psychological Status of Respiratory Function and Quality of Life of Patients with Severe Pneumonia in the ICU.

Objective This study examines the effects of the 3S2E nursing management mode on patients with severe pneumonia in the intensive care unit's respiratory function, psychological status, and quality of life (ICU). Methods According to a random number table, 82 ICU patients with severe pneumonia who were admitted between March 2021 and March 2022 were enrolled and assigned to the control and observation class (n = 41, respectively) in a 1 : 1 ratio. The observation class added 3S2E manner in addition to ordinary breastfeeding, whereas the control class received treatment in the usual nursing mode. The two groups' preintervention and postintervention times for mechanical ventilation, white blood cell count (WBC) recovery, duration of hospital stay, problems, respiratory function, psychological state, and living quality were compared. Results Fever time abatement, mechanical ventilation time, WBC recovery time, and length of hospital stay in the observation category were found to be shorter in comparison with the control class (P < 0.05). In contrast to the other group, the observation group had fewer issues (P < 0.05). Both teams' oxygenation indices and SaO2 were higher after the intervention (P < 0.05), with the observation team's index being higher than the control group's index. The total SAS and SDS scores of the two groups were less in the postintervention period than in the preintervention period, with the observational class having lower postintervention SAS and SDS ratings than the comparison group (P < 0.05). The postintervention ratings in the observation class were higher than those in the control, and the World Health Organization Quality of Life (WHOQOL) scale scores in the 2 categories were greater after the intervention than they were before (P < 0.05). Conclusion 3S2E nursing management model improves respiratory function, alleviates negative emotions, and improves living quality in ICU patients with severe pneumonia.

Efficacy and Prognosis of Ultrasound-Guided Percutaneous Catheter Drainage in Patients with Liver Abscess Complicated with Septic Shock.

Objective Currently, the therapeutic effect and outcomes of US-PCD in patients with liver abscess and septic shock remain unclear. This study is aimed at investigating the effects of ultrasound-guided percutaneous catheter drainage (US-PCD) on the prognosis of patients with liver abscess complicated with septic shock. Method We retrieved and assessed the data of 120 patients with liver abscess complicated with septic shock diagnosed at our hospital from January 2019 to March 2021. The patients underwent US-PCD in the observation group or conventional surgical incision and drainage in the control group. After treatment, we determined the levels of liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), and alkaline phosphatase (ALP) as well as the levels of inflammatory cytokines IL-6, IL-8, and TNF-α in serum using ELISA on postoperative days 0, 2, 4, and 6. The postoperative body temperature recovery, peripheral white blood cell count recovery, extubation, postoperative length of stay, and complications were recorded, with a 12-month follow-up to calculate their survival rate. Results After treatment, the ALT, AST, TBIL, DBIL, and ALP levels and inflammatory factor levels in the two groups were gradually reduced over time and returned to the normal range with a better recovery trend in the observation group. US-PCD was associated with better postoperative body temperature recovery, peripheral white blood cell count recovery, shorter extubation time, hospital stay, lower postoperative rate, and a higher survival rate. Conclusion US-PCD may be effective in treating liver abscess and can significantly improve the prognosis of patients.

Abstract 841: Mutant Trp53 R172H has gain-of-function or dominant-negative effects in response to hematopoietic stressors in mice

Abstract Background: Missense mutations of the TP53 gene frequently occur in patients with myelodysplastic syndrome and acute myeloid leukemia. The functional consequences of mutant p53 expression on hematopoiesis remain incompletely studied. Whether TP53 mutations confer a loss-of-function, gain-of-function, or dominant-negative effect in response to chemotherapies has not been fully explored. One of these hotspot mutations is a G-to-A substitution at nucleotide 525 of TP53, which codes for an Arg175His (R175H) substitution. Thus, we characterized hematopoiesis in Trp53R172H constitutive knock-in mice, corresponding to R175H TP53 mutation in patients, and compared the results to Trp53 knock-out and control mice. Methods: Five genotypes of mice were analyzed (Trp53+/+ [WT], Trp53R172H/+, Trp53R172H/R172H, Trp53+/-, and Trp53-/-). Frequencies of peripheral blood (PB) and bone marrow (BM) cells were measured by flow cytometry and fluorouracil (5-FU) and N-ethyl-N-nitrosourea (ENU) were used as hematopoietic stressors. Results: There was no change in the PB counts or lineage distribution of mature PB and BM cells in Trp53R172H/+ and Trp53R172H/R172H mice compared to WT or Trp53 knock-out mice at 8-15 weeks of age. We found that expression of Trp53R172H mutation in mice does not cause hematopoietic stem cell (HSC) expansion under basal conditions, in contrast to heterozygous and homozygous deletion of Trp53, but does confer a functional advantage to HSCs in a competitive repopulation assay. Trp53R172H HSCs expand further following ENU exposure, similar to Trp53-/- cells and consistent with a dominant-negative effect of Trp53R172H. Mechanistically, mutant p53R172H has a dominant-negative effect on p21-induced expression following ENU treatment. Repeated 5-FU injections drive proliferation of progenitors. To test the hematopoietic cell-intrinsic effects of mutant p53R172H on white blood cell count recovery, we exposed mice reconstituted with Trp53+/+, Trp53+/-, Trp53-/- or Trp53R172H/+ BM cells to a single dose of 5-FU and followed mice weekly for a month. Trp53R172H/+ mice were least affected by the 5-FU challenge and showed the fastest and largest recovery of WBC count compared to Trp53+/+, Trp53+/- and Trp53-/- mice. These results demonstrate that mutant p53R172H confers a gain-of-function property following 5-FU exposure that was not seen with deletion of Trp53. Conclusion: Our data suggest that in vivo expression of mutant Trp53R172H has minimal effects on basal hematopoiesis. However, mutant Trp53R172H induces either a gain-of-function or a dominant-negative effect depending on the type of hematopoietic stress and hematopoietic phenotype being observed. Overall, our results indicate that the functional consequences induced by various Trp53 mutations (e.g., deletion and point mutation) are not identical, but are influenced by the type of hematopoietic stress. Citation Format: Tuoen Liu, Tanzir Ahmed, Michael O. Alberti, Brian A. Wadugu, Jin Shao, Sarah Grieb, Grace Przybyl, Matthew Ndonwi, Matthew J. Walter. Mutant Trp53 R172H has gain-of-function or dominant-negative effects in response to hematopoietic stressors in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 841.

Effects of Prophylactic Administration of Granulocyte Colony-Stimulating Factor on Peripheral Leukocyte and Neutrophil Counts Levels After Chemotherapy in Patients With Early-Stage Breast Cancer: A Retrospective Cohort Study.

BackgroundBoth chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) frequently occur and can lead to dose-limiting toxicity and even fatal chemotherapy side effects. The prophylactic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF), including pegylated rhG-CSF (PEG-rhG-CSF), significantly reduces the risks of CIN and FN during chemotherapy in early-stage breast cancer (ESBC) patients. However, whether the prophylactic use of granulocyte colony-stimulating factor (G-CSF), especially PEG-rhG-CSF, can influence white blood cell (WBC) counts and absolute neutrophil counts (ANCs) after finishing the chemotherapy remains unknown. Therefore, exploring the development and recovery tendency of WBC counts and ANCs during and after chemotherapy is crucial.ObjectiveWe aimed to investigate the variation tendency and recovery of WBC counts and ANCs during and after chemotherapy and evaluate the independent factors influencing leukopenia and neutropenia lasting longer after chemotherapy. We also aimed to provide individualized prophylactically leukocyte elevation therapy for breast cancer patients.MethodsThis single-center retrospective cohort study evaluated 515 ESBC patients who received rhG-CSF or PEG-G-CSF for prophylaxis after adjuvant or neoadjuvant chemotherapy. Blood test reports were analyzed during chemotherapy, and on a 12-month follow-up period after finishing the chemotherapy. The WBC counts and ANCs were measured to assess their variation tendency characteristics and to identify independent factors that influenced the occurrence of leukopenia and neutropenia lasting longer than 12 months after chemotherapy.ResultsProphylaxis with rhG-CSF or PEG-rhG-CSF kept the mean values of WBC counts and ANCs within the normal range during chemotherapy, but a significant difference in WBC levels was detected before the end of the last chemotherapy compared to the prechemotherapy period (baseline) (p < 0.001). During the 12-month follow-up after the end of the last chemotherapy, WBC counts and ANCs gradually recovered, but the group that used only PEG-rhG-CSF (long-acting group, p WBC = 0.012) or rhG-CSF (short-acting group, p WBC = 0.0005) had better leukocyte elevation effects than the mixed treatment group (PEG-rhG-CSF mixed rhG-CSF). Besides, the short-acting group had a better neutrophil elevation effect than the longer-acting (p ANC = 0.019) and mixed (p ANC = 0.002) groups. Leukopenia was still present in 92 (17.9%) patients and neutropenia in 63 (12.2%) 12 months after the end of the last chemotherapy. The duration of leukopenia over 12 months was closely associated with the baseline WBC level (p < 0.001), G-CSF types (p = 0.027), and surgical method (p = 0.041). Moreover, the duration of neutropenia over 12 months was closely related to the baseline ANC (p < 0.001), G-CSF types (p = 0.043), and molecular typing (p = 0.025).ConclusionThe prophylactic application of G-CSF effectively stabilized the WBC counts and ANCs during chemotherapy in ESBC patients. Nevertheless, the recovery of WBC counts and ANCs after chemotherapy varied between different G-CSF treatment groups. The risk of leukopenia and neutropenia persisting for more than 12 months after chemotherapy was associated with G-CSF types, the baseline level of WBC count/ANCs, surgical method, and molecular typing.

Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies.

While cigarette smoking is a well-recognized cause of elevated white blood cell (WBC) count, studies on longitudinal effect of smoking cessation on WBC count are limited. We attempted to determine causal relationships between smoking and elevated WBC count by retrospective cross-sectional study consisting of 37,972 healthy Japanese adults who had a health check-up between April 1, 2008 and March 31, 2009 and longitudinal study involving 1730 current smokers who had more than four consecutive annual health check-ups between April 1, 2007 and March 31, 2012.In the cross-sectional study, younger age, male gender, increased body mass index, no alcohol habit, current smoking, and elevated C-reactive protein level were associated with elevated WBC count. Among these factors, current smoking had the most significant association with elevated WBC count. In subgroup analyses by WBC differentials, smoking was significantly associated with elevated counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Ex-smoking was not associated with elevated WBC count. In the longitudinal study, both WBC and neutrophil counts decreased significantly in one year after smoking cessation and remained down-regulated for longer than next two years. There was no significant change in either WBC or neutrophil count in those who continued smoking.These findings clearly demonstrated that current smoking is strongly associated with elevated WBC count and smoking cessation leads to recovery of WBC count in one year, which is maintained for longer than subsequent two years. Thus, current smoking is a significant and reversible cause of elevated WBC count in healthy adults.

Clinical resarch of decitabine combined with modified CAG regimen for treatment of relapsed or refractory acute myeloid leukemia

This study was to investigate the therapeutic effectiveness and side effect of decitabine combined with modified CAG regimen for relapse or refractory patients with acute myeloid leukemia. Ten patients suffered from relapsed or refractory acute myeloid leukemia from January 2013 to July 2013 were analyzed retrospectively, and the clinical characteristics, therapeutic effectiveness, side effect were observed. Among 10 patients 7 patients were males and 3 patients were females, the ratio of male to female was 7:3, median age was 45 (17-61) years. After treatment by using decitabine combined with modified CAG regimen, 7 patients achived complete remission, 1 patient achived partial remission, 2 patient did not achieve remission, the overall remission rate was 80% (8/10), the median time of white blood cell count recovery was 18.5 (5-28) days, median time of platelet level recovery was 19 (12-29) days. The main side effects of treatment were myelosuppression. There was no new lung infection in all cases, one case died of exacerbation of primary lung infection after therapy. The treatment of decitabine combined with modified CAG regimen for relapsed and refractory AML shows high response rate, low side effects, so it worthy to further clinical study.

The effect of comfort nursing on patients with acute severe pancreatitis

Objective To investigate the effect of comfort nursing on patients with acute severe pancreatitis .Methods A total of 100 cases of patients with acute severe pancreatitis were divided into two groups , in which 50 patients in the observation group were taken comfort nursing intervention , while the control group of 50 patients taking conventional cares measures .Results After treatment , the total effective rate of the observation group was 96.00%, significantly higher than that of the control group （ P〈0.05 ） , the observation group with abdominal pain and bloating relief time , urine amylase and white blood cell count recovery time were significantly better than those in the control group （ P〈0.05 ） , nurses attitude , level of care , health education and psychological care nursing satisfaction in the observation group was 98.0%.100.0%, 96.0%and 100.0%respectively , all were significantly higher than those in the control group , and the differ-ences were statistically significant （ P〈0.05 ） .Conclusions Comfort care measures can effectively improve the clinical efficacy in patients with acute severe pancreatitis , help restore a patient＆#39;s prognosis and improve patient satisfaction , and it is worthy of clinical application . Key words: Comfort Care; Acute severe pancreatitis

White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome

To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1-3 months after HCT was categorized as low (<2), normal (2-10), and high (>10 × 10(9) cells/L). Overall survival (OS) and progression-free survival (PFS) were lower for patients with low or high WBC at 1-3 months after HCT (P < 0.0001). We developed a predictive three-group risk model based on the pattern of WBC recovery early after HCT. Five-year OS was 47, 30, and 15% (P < 0.0001) and 5-year PFS was 39, 22, and 14% for patients in the three different risk groups (P < 0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression-free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials.

Clinical and Laboratory Factors Influencing The Probability Of Complete Remission In AML Patients With Positive Day 14 Bone Marrows

Abstract Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on day 14 (D14) post chemotherapy is considered an important predictor of achieving complete remission (CR). Our aim was to identify clinical and laboratory factors influencing the probability of CR in AML patients (pts) with positive D14 BM without receiving further chemotherapy. Methods Records of pts with AML treated between 1998 and 2011 were retrospectively reviewed to identify subjects with positive D14 BM who did not receive re-induction chemotherapy. The distribution of following variables such as age, white blood cell count (WBC) at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk was compared by the univariate analysis. Recovery BM status (positive vs. negative for disease) as the response variable and age, WBC at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk as explanatory variables were assessed by the logistic regression analysis. Poor risk AML was defined as the presence of adverse karyotype, treatment related disease or presence of antecedent hematologic disorder. Positive BM was defined as either cellularity ≥20% or ≥5% myeloblasts by IHC staining. CR was defined according to IWG 2003 criteria. Results 169/378 (44%) had a positive D14 BM after induction therapy and 92/169 (54%) did not receive re-induction chemotherapy. 68/92 (74%) underwent repeated BM evaluation at WBC recovery, which occurred 4-5 weeks after induction chemotherapy. Recovery BM showed refractory AML in 38/68 (56%) of cases. However, in 30/68 (44%) cases CR was achieved despite previously positive D14 BM. As demonstrated in Table 1, clinical and laboratory characteristics of the CR and refractory groups showed significant differences in the absolute percentage of D14 myeloblasts, abnormal vs. normal myeloblast phenotype, de novo vs. relapse disease status, and risk stratification. Higher blast percentage (P=.0016) was associated with significantly higher probability of having refractory AML and each 1% increase blasts on D14 BM increased the odds of refractory AML on recovery BM by 6% (OR=1.06 95% CI 1.022-1.099) (Figure 1) In contrast, no clear association between D14 BM cellularity and the recovery BM status was found. The results from the multivariate analysis were comparable with that from the univariate analysis. Blast percentage, disease status, and AML risk were strongly and jointly associated with the status of BM recovery. By using a logistic model including myeloblast percentage, myeloblast phenotype, disease status, and AML risk category we correctly predicted 31 refractory AML cases out of 38 (sensitivity = 82%) and we correctly predicted 23 CR cases out of 30 (specificity = 77%). For example, based on our formula, which incorporated blast percentage, disease status, and AML risk we estimated that in a patient with de novo, not a poor risk AML with 5% blasts on D14 BM the probability of positive recovery BM status was 6%, whereas in a patient with relapsed poor risk AML and 50% blasts on D14 BM the probability of positive recovery BM status was 98%. Conclusions Significant proportion of pts with positive D14 BM may achieve CR without subsequent chemotherapy administration. Low blast percentage, absence of phenotypically abnormal myeloblasts, de novo diagnosed AML, and absence of poor risk AML are associated with a significantly higher probability of CR. We developed a useful formula for predicting remission status in the setting of positive D14 BM that would be valuable in clinical trial protocols involving decision trees for re-induction chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Sirolimus: A Switch Option for Mycophenolate Mofetil–Induced Leukopenia in Renal Transplant Recipients

Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used to prevent acute and chronic rejection in kidney transplantation or for rescue therapy. One side effect of MMF is bone marrow toxicity, including leukopenia, which may necessitate drug withdrawal. We report 2 patients who underwent kidney transplantation and developed leukopenia while receiving MMF and safely switched to sirolimus. A 35-year-old woman underwent deceased donor kidney transplantation. She received basiliximab, tacrolimus, MMF, and a corticosteroid. On postoperative day (POD) 75, her white blood cell (WBC) count was 1800/μL. A 44-year-old women underwent deceased donor kidney transplantation and received basiliximab, tacrolimus, MMF, valganciclovir, and a corticosteroid. On POD 88, her WBC count was 1320/μL. MMF was switched to sirolimus, resulting in recovery of WBC count without rejection. Switch from MMF to sirolimus is safe and favorable in MMF-induced leukopenia in renal transplant recipient.

Use of CXCR4-antagonist for haematopoietic stem cell mobilization in HIV-infected patients with haematological malignancies

Use of CXCR4-antagonist for haematopoietic stem cell mobilization in HIV-infected patients with haematological malignancies

Impact of White Blood Cell Count Recovery On Clinical Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation

AbstractAbstract 4136 Background:Studies have shown that absolute lymphocyte count (ALC) early after allogeneic hematopoietic stem cell transplantation (HSCT) affects clinical outcomes. We hypothesize that the white blood cell (WBC) count at 1 month after HSCT may also predict transplant outcomes. Methods:1115 adult patients undergoing allogeneic HSCT from 2003 through 2009 at Dana-Farber/Brigham and Women’s Hospital were analyzed. The median age was 51 yrs (range 18–74); median follow up time among survivors was 4.3 years (range 1.1–9.2); 596 patients received reduced intensity conditioning (RIC) and 519 received myeloablative conditioning (MAC). Using the restricted cubic spline estimates on the log relative hazard over WBC at 1 month post HSCT, WBC was categorized as: low (0-<2), normal (2–10), and high (>10×109 cells/L). Results:The outcomes are summarized in the table and figure below. One-year OS was 52%, 71%, 48% for low, normal, high WBC at 1 month post HSCT, respectively, (p<0.0001) and 1-year PFS was 39%, 56%, and 44% for low, normal, high WBC, respectively (p<=0.0001). One year cumulative incidence of NRM was 15%, 5.2%, 9.1% for low, normal, high WBC (p=0.008 for low vs normal, p=0.33 for high vs normal) in RIC and 23%, 15%, 28% for low, normal, high WBC (p=0.28 for low vs normal, p=0.001 for high vs normal) in MAC. One year cumulative incidence of relapse was 51%, 44%, 58% for low, normal, high WBC (p=0.49 for low vs normal, p=0.04 for high vs normal) in RIC but 27%, 22%%, 23% for low, normal, high WBC (p=n.s.) in MAC. In multivariable multinomial logistic regression analysis, age (OR=0.94, p=0.004) and sirolimus containing GVHD prophylaxis (OR=3.3, p=0.044) in MAC, and mismatched donor type (OR=3.0, p=0.03) in RIC were the risk factors for low WBC; AML/CML (OR=8.2, p=0.009), CLL (OR=13.9, p=0.0036) in RIC and high disease-relapse index (ref. Armand et al, Blood, 2012) (OR=3.26, p=0.04) were risk factors for high WBC. In multivariable Cox model adjusting for other prognostic factors, both low and high WBC at 1 month were associated with poor OS (Low WBC: HR 1.59, p=0.01; High WBC: HR 1.85, p=0.007) and PFS (low WBC: HR 1.59, p=0.008; high WBC: HR 1.68, p=0.017) in RIC and high WBC at 1 month was associated with both poor OS (HR 1.93, p<0.0001) and PFS (HR 1.7, p=0.0006) in MAC. Furthermore, low or high WBC was associated with viral or fungal infection within 100 days of HSCT (viral: 27%, 9%, 9%,p=0.019 in MAC; 9%, 4%, 15%, p=0.01 in RIC; fungal: 27%, 6%, 9%,p=0.0006 in MAC; 2%, 2%, 9%, p=0.046 in RIC). In the MAC cohort, high WBC at 1 month was associated with development of subsequent grade II-IV acute GVHD: 41%, 39%, 51% for low, normal, (p<0.001). In the RIC cohort, only 48% in low (p<0.001) and 54% in high WBC (p=0.02) achieved ≥90% donor chimerism by day 30 post HSCT compared to 76% of patients in normal WBC, suggesting that the abnormal WBC reflects poor donor engraftment or persistence of underlying disease. There was a weak correlation between WBC and ALC at 1 month (correlation coefficient = 0.46). Low ALC is associated with poor outcome, but not high ALC. Conclusion:Out data suggest that WBC at 1 month after allogeneic HSCT predicts transplant outcomes independent of ALC and chimerism.WBCNNRM (%)p-valueRelapse (%)p-valuePFS (%)p-valueOS (%)p-valueRIC0-<247150.008510.49340.01510.0022-105165.2ref44ref50ref72ref>10339.10.33580.04330.002480.0003MAC0-<222230.28270.46500.006550.0032-1041615ref22ref63ref70ref>1081280.001230.65480.000548<0.0001Combined0-<269170.03430.12390.000152<0.00012-109329.4ref34ref56ref71ref>1011423<0.0001330.9444<0.000148<0.0001 [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Mice with heterozygous deficiency of lipoic acid synthase have an increased sensitivity to lipopolysaccharide-induced tissue injury

Alpha-lipoic acid (1, 2-dithiolane-3-pentanoic acid; LA), synthesized in mitochondria by LA synthase (Lias), is a potent antioxidant and a cofactor for metabolic enzyme complexes. In this study, we examined the effect of genetic reduction of LA synthesis on its antioxidant and anti-inflammatory properties using a model of LPS-induced inflammation in Lias+/- mice. The increase of plasma proinflammatory cytokine, TNF-alpha, and NF-kappaB at an early phase following LPS injection was greater in Lias+/- mice compared with Lias+/+ mice. The circulating blood white blood cell (WBC) and platelet counts dropped continuously during the initial 4 h. The counts subsequently recovered partially in Lias+/+ mice, but the recovery was impaired totally in Lias+/- mice. Administration of exogenous LA normalized the recovery of WBC counts in Lias+/- mice but not platelets. Enhanced neutrophil sequestration in the livers of Lias+/- mice was associated with increased hepatocyte injury and increased gene expression of growth-related oncogene, E-selectin, and VCAM-1 in the liver and/or lung. Lias gene expression in tissues was 50% of normal expression in Lias+/- mice and reduced further by LPS treatment. Decreased Lias expression was associated with diminished hepatic LA and tissue oxidative stress. Finally, Lias+/- mice displayed enhanced mortality when exposed to LPS-induced sepsis. These data demonstrate the importance of endogenously produced LA for preventing leukocyte accumulation and tissue injury that result from LPS-induced inflammation.

Bilateral Marginal Keratitis Associated With Engraftment Syndrome After Hematopoietic Stem Cell Transplantation

To report the first case of bilateral marginal keratitis in the setting of engraftment syndrome in a patient who had undergone hematopoietic stem cell transplantation. A 63-year-old man with a history of myelodysplastic syndrome presented with a 5-day history of red eyes. Two weeks before presentation, the patient had received a matched unrelated donor peripheral blood stem cell transplant and subsequently developed engraftment syndrome with a rapid white blood cell count recovery, noninfectious fever, skin rash, and shortness of breath. Ocular symptoms coincided with the timing of the white blood cell recovery. On examination, vision was 20/20 OU with +1 conjunctival injection with bilateral corneal subepithelial infiltrates in the periphery, particularly in areas of corneal pannus from previously existing contact lens-related neovascularization. There was no evidence of blepharitis, meibomian gland dysfunction, or uveitis. Ocular bacterial and viral cultures were negative, and a conjunctival biopsy was negative for viral inclusions or ocular graft-versus-host disease. The patient was initially treated with topical antibiotics for 2 days without any improvement and treated with topical corticosteroids 4 times daily. Examination 7 days after starting topical corticosteroids showed complete resolution of the marginal keratitis. Engraftment syndrome is notable for a rapid recovery of the white blood cell count after hematopoietic stem cell transplantation. Patients who present with presumed conjunctivitis in the setting of autologous and allogeneic stem cell transplantation should be evaluated for engraftment syndrome-related marginal keratitis.

Parenteral nutrition is not superior to replacement fluid therapy for the supportive treatment of chemotherapy induced oral mucositis in children

Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis.

Mobilização e coleta das células progenitoras hemopoiéticas periféricas para transplante autólogo em pacientes onco-hematológicos

Abstract This is a prospective and controlled studyto analyse the mobilisation and collection ofpluripotent precursor cells in order to assess thepredictive factors related to CD34 + yield inpatients affected by haematologicalmalignancies. From Jan/98 to Aug/99, 41patients (26M/15F), with a median age of 35years (12 – 59), underwent 115 procedures forCD34 + cells collection. The diagnoses were: 21(51.2%) non-Hodgkin lymphomas (NHL); 15(36.6%) Hodgkin disease (HD); 2 (4.9%) chronicmyeloid leukaemia (CML) and 3 (7.3%) multiplemyeloma (MM). Patients were mobilised usingchemotherapy (Cyclophosphamide (CY) 4g/m 2 ,CY7g/m 2 , Etoposide 2g/m 2 , “DHAP” or “Mini-Ice”regimens) followed by G or GM-CSF.Leukapheresis was started when peripheral whiteblood cell count (WBC) reached 1.0x10 9 /L. Theaim was to collect at least 5x10 6 CD34 + cells/Kgof body weight. Eleven (9.5%) procedures wereperformed in Dideco Vivacell BT 798 CE/A; thirtynine (33.9%) in Baxter CS 3000 plus and sixty-five (56.5%) in Fresenius AS 104 equipment. Weanalysed the following variables: age, diagnosis,CT mobilisation regimen, growth factor, previousCT lines, prior RT, WBC recovery and numberof apheresis. For statistical analysis, we useddescriptive statistics, Gaussian adjustment(goodness of fit), univariate analysis andmultivariate analysis (ANOVA), Pearson’scorrelation and regression with bivariatedGaussian curves. We performed a median ofthree procedures per patient (1-6).The medianof days needed for WBC to reach 1.0 x 10

Myeloablative chemoradiotherapy and autologous bone marrow infusions for treatment of neuroblastoma: factors influencing engraftment

Bone marrow harvested from cancer patients for autologous bone marrow reinfusion (ABMR) after myeloablative treatment may be injured, in both its proliferating and stromal cell pools, by either previous treatment or manipulation at the time of harvest. We have examined the relative effects of seven covariates on hematologic recovery after ABMR in children with neuroblastoma (NBL) using univariate and step-up analysis. We measured recovery by times to achieve (1) white blood cell counts greater than 1,000/microL; (2) absolute neutrophil counts greater than 500/microL; and (3) platelet counts greater than 20,000/microL without transfusion. In univariate analysis, recovery was significantly associated with the amount of prior chemotherapy and the interval between last chemotherapy and marrow harvest. Patient sex, the number of granulocyte-macrophage colonies infused, harvest-to-freeze interval, and use of purging were marginally associated. After adjusting for potential confounders in a multivariate model, the amounts of chemotherapy and granulocyte-macrophage colonies infused were independently significant predictors of time to total white blood cell count recovery; chemotherapy courses and chemo-to-harvest interval were predictors of neutrophil count recovery; and sex, use of purging, and harvest-to-freeze interval were marginal predictors of platelet recovery. The speed of hematologic recovery after ABMR seems to depend mainly on pre-existing factors and marginally on manipulation of the marrow after harvest. These factors may affect both proliferating and stromal cell pools.

Myeloablative Chemoradiotherapy and Autologous Bone Marrow Infusions for Treatment of Neuroblastoma: Factors Influencing Engraftment

Abstract Bone marrow harvested from cancer patients for autologous bone marrow reinfusion (ABMR) after myeloablative treatment may be injured, in both its proliferating and stromal cell pools, by either previous treatment or manipulation at the time of harvest. We have examined the relative effects of seven covariates on hematologic recovery after ABMR in children with neuroblastoma (NBL) using univariate and step-up analysis. We measured recovery by times to achieve (1) white blood cell counts greater than 1,000/microL; (2) absolute neutrophil counts greater than 500/microL; and (3) platelet counts greater than 20,000/microL without transfusion. In univariate analysis, recovery was significantly associated with the amount of prior chemotherapy and the interval between last chemotherapy and marrow harvest. Patient sex, the number of granulocyte-macrophage colonies infused, harvest-to-freeze interval, and use of purging were marginally associated. After adjusting for potential confounders in a multivariate model, the amounts of chemotherapy and granulocyte-macrophage colonies infused were independently significant predictors of time to total white blood cell count recovery; chemotherapy courses and chemo-to-harvest interval were predictors of neutrophil count recovery; and sex, use of purging, and harvest-to-freeze interval were marginal predictors of platelet recovery. The speed of hematologic recovery after ABMR seems to depend mainly on pre-existing factors and marginally on manipulation of the marrow after harvest. These factors may affect both proliferating and stromal cell pools.