Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion ...refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation. Of 167 patients included in this study, 101 received peripheral blood stem cell transplantation (PBSCT) and 66 received umbilical cord blood transplantation (UCBT). Overall, the percentage of platelet transfusions with a 14-h CCI lower than 5000 was 59.3%, being these data significantly higher for UCBT (67.6%) than for PBSCT (31.0%). Seventy-eight percent of patients underwent UCBT become refractory, while 38.6% of patients who received PBSCT were refractory. Factors associated to platelet refractoriness were lower CD34+ cell dose infused, higher number of antibiotics used, presence of anti-HLA I antibodies, and reduced-intensity conditioning regimen. Platelet refractoriness is a frequent and complex adverse event and remains a therapeutic challenge in the management of patients undergoing HSCT. There is a higher rate of platelet refractoriness in patients who received UCBT as compared to patients who received PBSCT.
CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and ...transplant-related mortality (TRM) in 113 patients with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m−2; VP-16, 750 mg m−2; and high-dose BCNU, 800 mg m−2) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m−2; VP-16, 800 mg m−2; cytarabine, 800 mg m−2; melphalan, 140 mg m−2). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.
During the COVID-19 crisis it was necessary to generate a specific care network and reconvert operating rooms to attend emergency and high-acuity patients undergoing complex surgery. The aim of this ...study is to classify postoperative complications and mortality and to assess the impact that the COVID-19 pandemic may have had on the results.
this is a non-inferiority retrospective observational study. Two different groups of surgical patients were created: Pre-pandemic COVID and Pandemic COVID. Severity of illness was rated according to the Diagnosis-related Groups (DRG) score. Comparisons were made between groups and between DRG severity score-matched samples. Non-inferiority was set at up to 10 % difference for grade III to V complications according to the Clavien-Dindo classification, and up to 2 % difference in mortality.
A total of 1649 patients in the PreCOVID group and 763 patients in the COVID group were analysed; 371 patients were matched for DRG severity score 3-4 (236 preCOVID and 135 COVID). No differences were found in relation to re-operation (22.5 % vs. 21.5 %) or late admission to critical care unit (5.1 % vs. 4.5 %). Clavien grade III to V complications occurred in 107 patients (45.3 %) in the PreCOVID group and in 56 patients (41.5 %) in the COVID group, and mortality was 12.7 % and 12.6 %, respectively. During the pandemic, 3 % of patients tested positive for Covid-19 on PCR: 12 patients undergoing elective surgery and 11 emergency surgery; there were 5 deaths, 3 of which were due to respiratory failure following Covid-19-induced pneumonia.
Although this study has some limitations, it has shown the non-inferiority of surgical outcomes during the COVID pandemic, and indicates that resuming elective surgery is safe.
Clinicaltrials.gov identifier: NCT04780594 .
Key Clinical Message
Glanzmann thrombasthenia is a rare bleeding disorder that can present life‐threatening bleeding. Our patients develop antiplatelet antibodies that become refractory to any ...pharmacological treatment. Allogeneic hematopoietic stem‐cell transplantation is the only currently curative procedure, but has major risks mainly in adult; indeed, our patient died.
Glanzmann thrombasthenia is a rare bleeding disorder that can present life‐threatening bleeding. Our patients develop antiplatelet antibodies that become refractory to any pharmacological treatment. Allogeneic hematopoietic stem‐cell transplantation is the only currently curative procedure, but has major risks mainly in adult; indeed, our patient died.
Infectious complications are a major cause of morbidity and mortality in patients who undergo autologous stem cell transplantation (ASCT). We examined 476 patients with hematologic malignancies (401) ...or solid tumors (75) who underwent ASCT between February 1990 and May 2005. Anti-infectious prophylaxis consisted of different combinations of ciprofloxacin, cotrimoxazole, fluconazole, aerosolized amphotericin B, acyclovir, and intravenous immunoglobulins. Overall, 454 patients (95%) developed fever in the first 60 days after ASCT. In the majority of patients, initial antibiotic therapy consisted of broad-spectrum beta-lactamic with or without amikacin. A glycopeptide was administered as initial therapy in 86 cases. Overall, there were 132 (29%) clinically documented infections (37 pneumonias), 79 (17%) microbiologically documented infections (65 bacteremias), and 243 (54%) fevers of unknown origin. Coagulase-negative staphylococci (18, 25%) and E coli (18, 25%) were the organisms most frequently isolated. The pattern of infection did not change throughout the study except for a significantly higher incidence of bacteremia due to gram-positive bacteria in the first 5 years of the study. Infection-related mortality was 5% (21 cases), with pneumonia the most frequent cause of death. ASCT should be considered a low-risk procedure, although new therapeutic approaches for patients developing severe respiratory infections are still needed.
Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous ...analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable
WT1
expression levels, low
TET2
, and low
IER3
gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were:
WT1
detection (
p
= 0.014), low
TET2
(
p
= 0.002), and low
IER3
expression (
p
= 0.025).
WT1
detection (
p
= 0.006) and low
TET2
(
p
= 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were:
WT1
detection (
p
= 0.003), high
EVI1
expression (
p
= 0.001), and undetectatable
p15-CDKN2B
(
p
= 0.037).
WT1
expressers were associated with adverse clinical–biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable
WT1
expression levels, and low
TET2
and low
IER3
expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However,
WT1
was the only molecular marker displaying an independent prognostic value in both OS and TFS.
Abstract Total nucleated (TNCs) and CD34+ cells are considered major determinants of outcome after umbilical cord blood (UCB) transplantation but the effect of other cell subtypes present in the ...graft is unknown. This single-center cohort study included patients with hematological malignancies who received UCB transplantation after a myeloablative conditioning regimen. UCB units were primarily selected according to cell content, both TNCs and CD34+ cells, and also according to the degree of HLA matching. Counts of several cell subtypes of the infused UCB unit, together with HLA disparities and other patient- and transplantation-related characteristics, were analyzed by multivariable methodology for their association with myeloid and platelet engraftment, graft-versus-host disease, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Two hundred patients (median age, 32 years) were included in the study. In multivariable analyses, a greater number of CD8+ cells was significantly associated with better results for myeloid ( P = .001) and platelet ( P = .008) engraftment, NRM ( P = .02), DFS ( P = .007), and OS ( P = .01). CD34+ cell content was predictive of myeloid engraftment ( P < .001). This study suggests that the outcome after UCB transplantation in adults with hematological malignancies could be better when UCB grafts had a greater CD8+ cell content.
Abstract 3803
A revised form of the International Prognostic Scoring System (IPSS-R) has recently been derived from a huge retrospective patient series (Greenberg et al, 2012), and a biologically ...upgraded version (IPSS-R “molecular”) is being worked out by the same group. The aim of this study was to evaluate the potential additive contribution of patient-related, as well as readily accessible peripheral blood disease-related prognosticators, to the IPSS-R prediction capability for estimating overall survival (OS) and progression into acute myeloid leukemia (AML) in MDS patients.
We prospectively recruited 266 MDS patients (Pts), from June 2006 to June 2010, in eight GESMD sites. The study was approved by the IRB at each study site and all Pts gave written informed consent. Cytological diagnosis and cytogenetic analysis followed standard operating procedures of the GESMD, ISCN guidelines and Schanz’s categorization. Sixty-six Pts were excluded (MDS not confirmed 3, secondary MDS 6, CMML 40, lack of a valid karyotype 14 – w/o mitoses 10, not attempted 4-, duplicate 1, consent revocation 1). Finally 200 primary MDS cases (125 M/75 F; median age 76, range 31–91) were classified according to WHO-2008 (RC 11, RARS 13, RCMD 101, RAEB-1 30, RAEB-2 24, 5q- syndrome 15, hypoplastic MDS 1, unclassifiable 5), followed up until June 2012 (median follow-up 2.6 years, range 0.06–6.3) and categorized according to IPSS-R (Very Low 50, Low 80, Intermediate 33, High 25 and Very High 12). Fifty-five Pts received disease-modifying therapeutic strategies (DMTS) such as azacitidine (38), intensive chemotherapy w/o allo-BMT (17; in 6 Pts after AZA), or allo-BMT (13; in 7 after intensive chemotherapy). Forty-two Pts (21%) progressed into AML, 87 (43.5%) died and 13 (6.5%) were lost to follow-up. Median OS was 4.2 years. Age, comorbidity (as measured by Lee et al, 2006), performance status (ECOG), transfusion-dependence (according to Malcovati), serum LDH at diagnosis, ferritin, beta2-microglobulin, albumin, erythropoietin, plasma soluble p53-protein and interleukin-10 levels (ELISA), as well as peripheral blood WT1 gene expression (real-time PCR) were analyzed by testing the change in likelihood-ratio and the Akaike’s information criterion (AIC) in Cox models after adding each individual covariate to IPSS-R. The increased discriminating power of the expanded prognostic model over that of IPSS-R alone was evaluated by the Harrell’s C index and the R2explained variation. Replicability of the expanded prognostic model was tested by bootstrap re-sampling (1000 samples).
Addition of age (continuous) and ECOG (cutoff ≥2) to IPSS-R significantly improved the model’s prognostic power, as measured by the likelihood ratio test and the AIC, as well as the discriminating power (Harrell’s C increased from 0.70 to 0.75). Interestingly, addition of IL10 (cutoff ≥4.0 pg/mL) further improved the predictive power and reduced the residual variance (R2increased from 0.23 to 0.50). IL10 plasma levels were directly correlated with ferritin and transfusion dependence, and inversely correlated with hemoglobin. Bootstrap re-sampling predicted a replicability in eventual external validation series of 100%, 73%, 38% and 51%, respectively, for the covariates IPSS-R, age, ECOG and IL10. The IPSS-R category was the only predictor of progression into AML. Adjustment of the expanded prognostic model for exposure to DMTS, evaluated as a time-dependent covariate, had no relevant effect on the model’s predictive ability.
Patient's age, ECOG and plasma levels of IL10 at diagnosis add further information to the IPSS-R risk category in the prognostication of patients with MDS. As suggested by Greenberg et al. in their paper, our study confirms that some covariates not yet included in the IPSS-R may be of additional help for predicting the ultimate fate of MDS patients.
No relevant conflicts of interest to declare.
We analyzed the incidence, etiology, risk factors and outcomes of 49 episodes of pneumonia that developed in 326 adult patients undergoing autologous stem-cell transplantation (ASCT) from January ...1990 to December 2005. The median time for the onset of pneumonia after transplantation was 11 days (range 0 - 148). Empirical antibiotic therapy in patients with pneumonia consisted of piperacillin - tazobactam (20 cases, 49%), third-generation cephalosporin (11 cases, 27%) and carbapenem (8 cases, 19%). Multivariate analysis showed that a higher risk of pneumonia could be predicted for patients with myeloma (P = 0.006) and for patients with an absolute neutrophil count <0.5 × 109 L >7 days (P = 0.008). Cumulative incidence of transplant-related mortality at 6 months was 51% versus 8% for patients with or without pneumonia, respectively (P = 0.001). Pneumonia after ASCT is a severe complication more commonly observed in patients with myeloma and with prolonged duration of neutropenia.
Background: The prognostic significance of the expression pattern of certain cell surface markers in acute myeloid leukemia (AML) is controversial.
Objectives: Analyze the impact of the expression of ...certain cell surface markers on complete remission rate (CR) and relapse free survival (RFS), in a large series of adult patients with non-promyelocytic AML treated with intensive chemotherapy.
Methods: From 1989 to 2007, 451 adult patients (median age 57 years, range 15–80 years) diagnosed with non-promyelocytic AML, received first induction chemotherapy in our institution. Induction therapy consisted of the combination of cytarabine and anthracycline with or without a third agent in 95% of patients and other regimens in the remaining 5%. The post-remission treatment consisted of consolidation chemotherapy followed or not by stem cell transplantation. The inmunophenotypic analysis of bone marrow samples at diagnosis was evaluable in 395 patients (88%). Positivity was defined as more than 20% blasts expressing a specific antigen. It was possible to evaluate the percentage of positive blasts for the following antigens: CD33 (395 patients), CD13 (391), HLA-DR (382), CD14 (375), CD34 (364), CD7 (354), CD11b (350), CD4 (347), CD36 (343), CD15 (326), CD9 (321), CD2 (315), CD38 (250), CD71 (233), myeloperoxidase (MPX) (186), CD117 (178) and CD56 (173). We conducted a univariate and mutivariate analysis in order to define the impact of the expression of cell surface markers on CR rate and RFS.
Results: Overall, 256 patients (58.3%) achieved a CR. The following characteristics were associated with a lower probability of CR: age >60 years, performance status by means of ECOG scale ≥2, peroxidase staining in <75% of blasts, and high-risk karyotype (in all, p<0.001). The positivity of CD34 and the negativity of CD15 and MPX, were associated with a lower CR rate (p=0.005, p=0.04 and p<0.001, respectively), due to a higher rate of resistance (p<0.001, p=0.004 and p<0.001, respectively). Multivariate analysis showed that WBC >50×109/l, high-risk karyotype, CD34 positivity and MPX negativity were independent unfavourable factors for CR. The median follow-up of the cohort was 81 months and the overall RFS at 5 years was 35%. The following factors are associated with a lower RFS: CR achievement with 2 cycles (15% vs 37%, p<0.001), age >60 years (16% vs 44%, p<0.001), peroxidase staining in <75% of blasts (26% vs 49%, p=0.001), high-risk karyotype (0% vs 39%, p=0.03), CD2 positivity (11% vs 40%, p=0.008) and MPX negativity (16% vs 40%, p=0.02). Multivariate analysis showed that age >60 years, CR achievement with 2 cycles and MPX negativity were independent unfavourable factors for RFS.
Conclusion: The AML with an immature immunophenotype, like those with CD34 positivity or MPX negativity, shows a higher resistance to induction chemotherapy. We also have observed a shorter remission duration in those AML with CD2 positivity or MPX negativity.
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