Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma.

ABSTRACT: High-risk (HR) cytogenetics are associated with poor outcomes in newly diagnosed multiple myeloma (NDMM), and dedicated studies should address this difficult-to-treat population. The phase 2 study 2018-04 from the Intergroupe Francophone du Myelome evaluated feasibility of an intensive strategy with quadruplet induction and consolidation plus tandem transplant in HR transplant-eligible (TE) NDMM. HR cytogenetics were defined by presence of del(17p), t(4;14), and/or t(14;16). Treatment consisted of daratumumab-carfilzomib-lenalidomide-dexamethasone (D-KRd) induction, autologous stem cell transplantation (ASCT), D-KRd consolidation, second ASCT, and daratumumab-lenalidomide maintenance. The primary end point was feasibility. Fifty patients with previously untreated NDMM were included. Median age was 57. Del(17p), t(4;14), and t(14;16) were found in 40%, 52%, and 20% of patients, respectively. At data cutoff, the study met the primary end point with 36 patients completing second transplant. Twenty patients discontinued the study due to stem cell collection failure (n = 8), disease progression (n = 7), adverse event (n = 4), or consent withdrawal (n = 1). Grade 3 to 4 D-KRd induction/consolidation-related adverse events (>5% of patients) were neutropenia (39%), anemia (12%), thrombocytopenia (7%), and infection (6%). The overall response rate was 100% for patients completing second transplant, including 81% complete response. Premaintenance minimal residual disease (MRD) negativity rate (10-6) was 94%. After a median follow-up of 33 months, the 30-month progression-free survival (PFS) and overall survival were 80% and 91%, respectively. In conclusion, D-KRd with tandem transplant is feasible in patients with HR TE-NDMM and resulted in high response rates and PFS. This trial was registered at www.clinicaltrials.gov as #NCT03606577.

[Hypnotic pain management during ultrasound-guided infiltration of the hand]. / Gestion de la douleur par hypnose lors d'une infiltration écho-guidée de la main.

Ultrasound-guided infiltration, performed to relieve pain, is a common and sometimes painful procedure, particularly on the hand. This potential pain, induced by the treatment, can cause apprehension in patients prior to such a procedure. The rheumatology team at the departmental hospital center (CHD) in Vendée hypothesized that a hypnosis session, by creating an imaginary glove on the patient's painful hand prior to the procedure, could help reduce the pain felt, as well as anxiety.

Ropivacaine perineal infiltration for postpartum pain management in episiotomy repair: a double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To investigate whether perineal infiltration of ropivacaine after episiotomy would decrease the incidence of postpartum pain compared with placebo. DESIGN: Two-centre, double-blind, randomised, controlled trial. SETTING: Two French maternity units, October 2017 to April 2020. POPULATION: 272 women undergoing epidural analgesia with vaginal singleton delivery and mediolateral episiotomy at term (≥37 weeks) were randomly allocated perineal infiltration of ropivacaine (n = 135) or placebo (n = 137) in a 1:1 ratio before episiotomy repair. METHODS: Patients were followed at short term (12, 24, 48 h), mid-term (day 7) and long-term (3 and 6 months). MAIN OUTCOME MEASURES: The primary outcome was the rate of perineal pain, defined by a Numerical Pain Rating Scale (NPRS) exceeding 3/10, in the mid-term (day 7) postpartum period. Secondary outcomes were perineal pain (NPRS) and analgesic intake, quality of life (SF-36), postpartum depression (EPDS), pain neuropathic component (DN4) and sexual health (FSFI). RESULTS: Perineal pain occurred to an equal extent in the ropivacaine and placebo groups at day 7 (34.2% versus 30.4%, odds ratio 1.1, 95% confidence interval 0.7-1.8, p = 0.63). Similar results were recorded in the short and long term. High rates of dyspareunia and postpartum depression were documented in both groups. No differences were highlighted between the groups in terms of analgesic intake, adverse events, pain neuropathic component and postpartum quality of life. CONCLUSIONS: This study did not demonstrate any benefit of ropivacaine infiltration over placebo.

Epidemiology and microbiology of ventilator-associated pneumonia in COVID-19 patients: a multicenter retrospective study in 188 patients in an un-inundated French region.

BACKGROUND: The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear. METHODS: We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture. FINDINGS: We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013). INTERPRETATION: Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional. REGISTRATION: As an observational study, this study has not been registered.

Are corticosteroid injections needed after needling and lavage of calcific tendinitis? Randomised, double-blind, non-inferiority trial.

OBJECTIVE: Steroid injections are common after an ultrasound-guided puncture and lavage (UGPL) of calcific tendonitis of the rotator cuff. However, steroids may prevent calcification resorption and negatively affect tendon healing. Our study was designed to determine whether saline solution was non-inferior to steroids in the prevention of acute pain reactions in the week following UGPL. METHODS: This was a randomised, double-blinded, controlled non-inferiority trial with 12-month follow-up. We included 132 patients (66 in each group) with symptomatic calcification measuring more than 5 mm. Patients received 1 mL of saline or steroid (methylprednisolone 40 mg) in the subacromial bursa at the end of UGPL. Primary outcome was the maximal pain during the week following the procedure with a prespecified non-inferiority margin of 10 mm (0-100 visual analogue scale). Secondary outcomes included pain at rest and during activity, function (disabilities of the arm, shoulder and hand score) and radiological evolution of the calcification over the 12-month follow-up. RESULTS: The estimated mean difference in the first week's maximal pain between these two groups was 11.76 (95% CI 3.78 to 19.75). Steroids significantly improved VAS pain at rest and during activities, as well as function at 7 days and 6 weeks. They did not change the rate of calcification resorption, which occurred in 83% and 74% of patients at 12 months in the saline and steroid groups. CONCLUSION: Non-inferiority of saline when compared with steroids could not be established. However, steroid injection improved pain in the 6 weeks following the procedure, and function in the 3 months after, with no significant effect on calcification resorption. TRIAL REGISTRATION NUMBER: NTC02403856.

VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial.

The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27.

Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma.

This phase 1/2 dose-escalation study investigated the combination of carfilzomib with melphalan and prednisone (CMP) in patients aged >65 years with newly diagnosed multiple myeloma (MM). Melphalan and prednisone were administered orally on days 1 to 4; carfilzomib was IV administered on days 1, 2, 8, 9, 22, 23, 29, and 30 of a 42-day cycle. Patients received up to 9 cycles of CMP. In the phase 1 dose-escalation portion, the primary objectives were to determine the incidence of dose-limiting toxicities during the first cycle of CMP treatment to define the maximal tolerated dose (MTD) of carfilzomib. In the phase 2 portion, the primary objective was to evaluate the overall response rate (ORR) of CMP. In the phase 1 portion of the study, 24 patients received CMP at carfilzomib dosing levels of 20 mg/m(2), 27 mg/m(2), 36 mg/m(2), and 45 mg/m(2). The MTD was established as 36 mg/m(2). In the phase 2 portion of the study, 44 patients were enrolled at the MTD. Among 50 efficacy-evaluable patients treated at the MTD, the ORR was 90%. The projected 3-year overall survival rate was 80%. The combination of CMP was observed to be effective in elderly patients with newly diagnosed MM. This trial was registered at www.clinicaltrials.gov as #NCT01279694 (Eudract identifier 2010-019462-92).

Screening of esophageal varices by esophageal capsule endoscopy: results of a French multicenter prospective study.

BACKGROUND AND STUDY AIM: Esophageal video capsule endoscopy (ECE) is a new technique that allows examination of the esophagus using a noninvasive approach. The aim of this study was to compare ECE with esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal varices in patients with cirrhosis. PATIENTS AND METHODS: A total of 330 patients with cirrhosis and with no known esophageal varices were prospectively enrolled. Patients underwent ECE first, followed by EGD (gold standard). The endoscopists who performed EGD were blind to the ECE result. Patient satisfaction was assessed using a visual analog scale (maximum score 100). RESULTS: A total of 30 patients were excluded from the analysis because they did not undergo any endoscopic examinations. Patients (mean age 56 years; 216 male) had mainly alcoholic (45 %) or viral (27 %) cirrhosis. The diagnostic indices of ECE to diagnose and correctly stage esophageal varices were: sensitivity 76 % and 64 %, specificity 91 % and 93 %, positive predictive value 88 % and 88 %, and negative predictive value 81 % and 78 %, respectively. ECE patient satisfaction scored significantly higher than EGD (87 ±â€Š22 vs. 58 ±â€Š35; P < 0.0001). CONCLUSIONS: ECE was well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of ECE is not currently sufficient to replace EGD as a first exploration in these patients. However, due to its excellent specificity and positive predictive value, ECE may have a role in cases of refusal or contraindication to EGD. ECE might also improve compliance to endoscopic follow-up and aid important therapeutic decision making in the prophylaxis of bleeding. TRIAL REGISTRATION: EudraCT (ID RCB 2009-A00532-55) and ClinicalTrials.gov (NCT00941421).

Risk factors for hepatocellular carcinoma in Caucasian patients with non-viral cirrhosis: the importance of prior obesity.

BACKGROUND & AIMS: In patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender and the etiology of liver disease. Few studies are available in Caucasian patients with alcoholic or metabolic cirrhosis without viral hepatitis. METHODS: Cross-sectional clinical data from 905 HCV- and HBV-negative Caucasian patients with alcoholic or metabolic cirrhosis were prospectively collected in four French centres. The risk factors for HCC were identified by logistic regression analysis in the whole population and in a nested case-control study. RESULTS: The etiology of cirrhosis was alcoholic (48%), metabolic (7%) or mixed (45%). Patients were predominantly male (80%), mean age 62 years old and 31% had HCC. Mean body mass index (BMI) was 27 ± 5 and 30% were obese at inclusion. The maximum BMI reached throughout life was 31 ± 6 and 63% had been obese. Ninety percent of the population had daily alcohol consumption, 73% were smokers. Hepatocellular carcinoma was independently related to male gender (P < 0.0001), older age (P < 0.0001), past obesity (P = 0.007), diabetes (P = 0.037), abnormal levels of transaminases (P < 0.0001) and tobacco consumption (P = 0.007). The case-control study (200 HCC cases matched with 400 non-HCC cases for gender, age and Child-Pugh score) confirmed past obesity, tobacco and abnormal levels of transaminases. CONCLUSIONS: Beside diabetes, male gender and age, a past history of obesity, but not an existing overweight, as well as exposure to tobacco and elevated transaminases were three risk factors which could improve the strategy for HCC screening in Caucasian cirrhotic patients without hepatitis B or C.

Cervical ripening balloon compared with vaginal dinoprostone for cervical ripening in obese women at term: A prospective cohort study.

OBJECTIVE: To evaluate vaginal delivery in obese women who underwent cervical ripening at term using a dinoprostone vaginal insert or a cervical ripening balloon (CRB), and to assess maternal and neonatal morbidity according to the method. METHODS: A prospective cohort study including obese women with a live singleton fetus in cephalic presentation who required cervical ripening at term (≥37 weeks) for maternal and/or fetal disease using a dinoprostone vaginal insert or a CRB. The primary outcome was vaginal delivery. Secondary outcomes were a favorable cervix (Bishop score >6) after 24 h, the time from device insertion to delivery, and composite maternal and neonatal morbidity. RESULTS: In total, 135 consecutive women were analyzed (107 CRB, 79.3%; 28 dinoprostone vaginal insert, 20.7%). Vaginal delivery (86 [80.4%] after CRB vs 19 [67.9%] after dinoprostone vaginal insert; P = 0.248), favorable cervix within 24 h after device placement (52 [48.6%] vs 17 [60.7%]; P = 0.264), and maternal morbidity (12 [11.2%] vs 4 [14.3%]; P = 0.646) were similar between the groups. The time from device insertion to delivery also did not differ between the groups. Neonatal morbidity was significantly higher after the dinoprostone vaginal insert (11 [39.3%] vs 20 [18.7%]; P = 0.030). Cervical ripening using the dinoprostone vaginal insert, compared with the CRB, was significantly associated with neonatal morbidity (adjusted odds ratio 4.00, 95% confidence interval 1.34-12.5), but not with maternal morbidity (adjusted odds ratio 1.23, 95% confidence interval 0.30-4.38). CONCLUSIONS: Vaginal delivery, a favorable cervix after 24 h, the time from device insertion to delivery, and maternal morbidity did not significantly differ between the CRB and the dinoprostone vaginal insert for cervical ripening in obese women at term. Nevertheless, neonatal morbidity was significantly associated with the dinoprostone vaginal insert, compared with the CRB, among obese women who required cervical ripening at term.

Impact of the practice of touch-massage® by a nurse on the anxiety of patients with hematological disorders hospitalized in a sterile environment, a randomized, controlled study.

CONTEXT: In addition to curative care, supportive care is beneficial in managing the anxiety symptoms common in patients in sterile hematology unit. We hypothesize that personal massage can help the patient, particularly in this isolated setting where physical contact is extremely limited. The main objective of this study was to show that anxiety could be reduced after a touch-massage® performed by a nurse trained in this therapy. METHODS: A single-center, randomized, unblinded controlled study in the sterile hematology unit of a French university hospital, validated by an ethics committee. The patients, aged between 18 and 65 years old, and suffering from a serious and progressive hematological pathology, were hospitalized in sterile hematology unit for a minimum of three weeks, patients were randomized into either a group receiving 15-minute touch-massage® sessions or a control group receiving an equivalent amount of quiet time once a week for three weeks. In the treated group, anxiety was assessed before and after each touch-massage® session, using the State-Trait Anxiety Inventory questionnaire with subscale state (STAI-State). In the control group, anxiety was assessed before and after a 15-minute quiet period. For each patient, the difference in the STAI-State score before and after each session (or period) was calculated, the primary endpoint was based on the average of these three differences. Each patient completed the Rosenberg Self-Esteem Questionnaire before the first session and after the last session. RESULTS: Sixty-two patients were randomized. Touch-massage® significantly decreased patient anxiety: a mean decrease in STAI-State scale score of 10.6 [7.65-13.54] was obtained for the massage group (p ≤ 0.001) compared with the control group. The improvement in self-esteem score was not significant. CONCLUSION: This study provides convincing evidence for integrating touch-massage® in the treatment of patients in sterile hematology unit. TRIAL REGISTRATION: NCT02343965.

Impact of two endotracheal tube fixation on the incidence of peri-oral lesions: Elastic adhesive strips versus cord in a protective sheath. Study protocol for a cluster cross-over randomized trial.

BACKGROUND: Endotracheal tube fixation in ventilated patients must be appropriate to ensure security during mechanical ventilation and prevent skin lesions. The incidence of endotracheal tube-caused pressure ulcers ranges from 7% to 45%. Various endotracheal tube fixations are used in intensive care units (ICUs) worldwide. By pressure exercised on the skin, these systems could lead to mucosal and skin peri-oral lesions. The main objective of this study is to evaluate the impact of the two fixation systems most commonly used in French ICUs (adhesive elastic band versus fixation cord with PolyVinyl Chloride (PVC) sheath) on the incidence of these peri-oral skin lesions. METHODS: This studyis a multicenter, open-label, controlled, superiority, cluster cross-over randomized trial. 768 patients will be recruited in the 16 ICUs involved. The inclusion of patients will be carried out over two 12-month periods. Each site begins with one of the evaluated fixation systems: elastic adhesive tape or cord associated with a protective sheath. After a 4-month break, each site switches to the other fixation system. The primary outcome is the development of at least one peri-oral lesion during the first ten days of maintaining an orally inserted endotracheal tube. The presence of lesions is assessed by a blinded adjudication committee using photographs taken daily. DISCUSSION: This study is the first multicenter, randomized trial designed to evaluate the impact of elastic adhesive tape versus fixation cord with PVC sheath on the incidence of peri-oral lesions. The results will provide data which could change and standardize care practices. TRIAL REGISTRATION: https://www.clinicaltrials.gov. Reference number: NCT04819425.

Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma.

Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

Comparison of outcomes after two standards-of-care reduced-intensity conditioning regimens and two different graft sources for allogeneic stem cell transplantation in adults with hematologic diseases: a single-center analysis.

Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v. busulfan 3.6 mg/kg/day for 2 days + rabbit antithymocyte globulin 2.5 mg/kg/day for 2 days) supported by peripheral blood stem cells (PBSCs) and the TCF regimen (fludarabine 200 mg/m² for 5 days + cyclophosphamide 50 mg/kg for 1 day + low-dose [2 Gy] total body irradiation) supported by dUCB units are currently the most widely used RIC regimens in many centers and could be considered standard of care in adults eligible for an RIC allo-SCT. Here we compared, retrospectively, the outcomes of adults patients who received the FB2A2-PBSC RIC regimen (n = 52; median age, 59 years; median follow-up, 19 months) and those who received the dUCB-TCF RIC regimen (n = 39; median age, 56 years; median follow-up, 20 months) for allo-SCT between January 2007 and November 2010. There were no significant between-group differences in patient and disease characteristics. Cumulative incidences of engraftment, acute grade II-IV and chronic graft-versus-host disease were similar in the 2 groups. The median time to platelet recovery, incidence of early death (before day +100), and 2-year nonrelapse mortality were significantly higher in the dUCB-TCF group (38 days versus 0 days [P <.0001]; 20.5% versus 4% [P = .05], and 26.5% versus 6% [P = .02], respectively). The groups did not differ in terms of 2-year overall survival (62% for FB2A2-PBSC versus 61% for dUCB-TCF), disease-free survival (59% versus 50.5%), or relapse incidence (35.5% versus 23%). In multivariate analysis, the presence of a lymphoid disorder was associated with a significantly higher 2-year overall survival (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87; P = .02), whereas patients receiving a FB2A2-PBSC allo-SCT had a significantly lower 2-year nonrelapse mortality (hazard ratio, 0.24; 95% confidence interval, 0.1-0.7; P = .01). There were no factors associated with higher 2-year disease-free survival or lower relapse incidence. This study suggests that the dUCB-TCF regimen provides a valid alternative in adults lacking a suitable donor and eligible for RIC allo-SCT. Prospective and randomized studies are warranted to establish the definitive role of dUCB RIC allo-SCT in adults. In addition, strategies for decreasing nonrelapse mortality after dUCB RIC allo-SCT are urgently needed.

Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial.

In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in this study. Multivariate analysis showed that ISS stages 2 and 3 and achievement of response less than very good partial response (VGPR) both after induction therapy and after autologous stem cell transplantation were adverse prognostic factors for progression-free survival, the most important one being achievement of response less than VGPR after induction. Progression-free survival was significantly improved with bortezomib-dexamethasone induction therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared with vincristine-adriamycin-dexamethasone. In these 2 groups of patients, achievement of at least VGPR after induction was of major importance. This study is registered with EudraCT (https://eudract.ema.europa.eu; EUDRACT 2005-000537-38) and http://clinicaltrials.gov (NCT00200681).

Characterization of various blood and graft sources: a prospective series.

BACKGROUND: Studies comparing cell components of blood and graft sources are very scarce. We present here a thorough study examining the cellular content of various sources of blood and cell therapy products. STUDY DESIGN AND METHODS: We have prospectively compared by fluorescence-activated cell sorting analyses the cellular composition of three blood sources on the one hand--peripheral blood (PB; n = 10) versus granulocyte-colony-stimulating factor (G-CSF)-mobilized PB (GCSF-PB, n = 10) versus cord blood (CB, n = 10)--and of three graft sources on the other hand--unmanipulated bone marrow (uBM, n = 5) versus leukapheresis product (LP, n = 10) versus thawed CB graft (n = 7). RESULTS: All median absolute numbers of cell subsets were found significantly higher in GCSF-PB and LP, except for monocytoid dendritic cells (mDCs) in CB and uBM. The most impressive results were the median quantities of memory T and B lymphocytes but also of plasmacytoid DCs (pDCs) contained in LP compared to thawed CB graft, with ratios of 375, 318, and 247, respectively. The proportions of naive and CD4+/CD8- T cells, transitional B cells, and CD5+ and naive B lymphocytes were found significantly higher in CB samples while the proportions of mDCs and pDCs were found significantly lower. CONCLUSION: Our study shows strong differences in terms of quantitative and qualitative cellular composition between several blood or graft sources, possibly explaining the differences observed in terms of outcomes after transplant.

Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced-intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo-SCT).

This retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22-70)] who received a FB2 (fludarabine 120-150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced-intensity conditioning (RIC) allo-stem cells transplantations (SCT). With a median follow-up of 19 months (range: 2-53), the 2-yr overall survival, disease-free survival (DFS), relapse incidence, and non-relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2-yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm(3) ; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm(3) ) (2-yr OS: 81% vs. 44%, P = 0.007; 2-yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm(3) ) (2-yr OS: 76% vs. 50%, P = 0.03; 2-yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm(3) ; 2-yr OS: 80% vs. 45%, P = 0.004; 2-yr DFS: 76% vs. 42%, P = 0.01) at day +30 post-transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm(3) ) and a higher monocytes count (>590/mm(3) ) at day +30 post-transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo-SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo-SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo-SCT.

Predictors of efficacy for cervical ripening among the Bishop score criteria in nulliparous women at term.

OBJECTIVE: To determine predictors of efficacy for cervical ripening among the Bishop score criteria in nulliparous women at term. METHOD: Prospective observational study of nulliparous women with singleton term fetuses in vertex presentation, intact membranes, and an unfavorable cervix (Bishop score < 6) who underwent cervical ripening with a cervical-ripening balloon (CRB; n = 47) or dinoprostone vaginal insert (PG; n = 28). The authors analyzed Bishop score criteria (dilatation, effacement, fetal station, consistency, position) before and after device removal. Primary outcome was favorable cervix (Bishop score ≥ 6) after device removal. Secondary outcomes were vaginal delivery, modification of Bishop score criteria, and perinatal morbidity. RESULTS: Rates of favorable cervix after cervical ripening were similar between groups (66.7% with CRB vs. 59.3% with PG; P = 0.526). Vaginal delivery (76.6% vs. 78.6%; P = 0.843) and perinatal morbidity did not differ between groups. CRB appeared to be more effective than PG in increasing consistency (+0.7 ± 0.2 vs. +0.3 ± 0.2; P = 0.001) and dilatation of the cervix (+1.3 ± 0.3 vs. +0.9 ± 0.3; P = 0.005). No Bishop score criterion was found as a significant predictor for vaginal delivery. CONCLUSION: CRB seems to be more effective than PG in increasing the consistency and dilatation of the cervix. Efficacy of CRB and PG for vaginal delivery was similar.

Predictive Factors for Successful Cervical Ripening among Women with Gestational Diabetes Mellitus at Term: A Prospective Study.

The purpose of this prospective cohort study is to identify the predictive factors for vaginal delivery among women (n = 146) who underwent cervical ripening using a dinoprostone insert (PG) alone (13.7%), cervical ripening balloon (CRB) alone (52.7%), oral misoprostol (M) alone (4.1%), or repeated methods (R, 29.5%) for gestational diabetes mellitus (GDM) at term, and to analyze maternal and neonatal morbidity outcomes according to the method for cervical ripening. After cervical ripening, vaginal delivery occurred in 84.2% (n = 123) and was similar among groups (90.0% after PG, 83.1% after CRB, 83.3% after M, and 83.7% after R; p = 0.89). After a multivariable logistic regression analysis adjusted for potential confounders, the internal cervical os being open before cervical ripening was a predictor of vaginal delivery (adjusted odds ratio (OR) of 4.38, 95% confidence index (CI) of 1.62-13.3, p = 0.03), and previous cesarean delivery was a predictor of cesarean delivery (aOR of 7.67, 95% CI of 2.49-24.00, p < 0.01). Birthweight was also significantly associated with cesarean delivery (aOR of 1.15, 95% CI of 1.03-1.31, p = 0.02). The rates of maternal and neonatal morbidity outcomes were 10.9% (n = 16) and 19.9% (n = 29), respectively, and did not differ according to the mode of delivery and to the method used for cervical ripening. Identifying these specific high-risk women (previous cesarean delivery and internal cervical os being closed before cervical ripening) for cesarean delivery among women who underwent cervical ripening for GDM at term is important and practical for all physicians to make a decision in partnership with women.