Thiotepa,Fludarabine, and Busulfan Conditioning Regimen before T Cell–Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.     

Need for urodynamic evaluation as a regular follow-up tool in assessment of long-term urological outcomes in patients with sacrococcygeal teratoma

AimTo assess the long-term urologic outcomes in follow-up of patients of sacrococcygeal teratoma (SCT) using urodynamic study (UDS) in addition to clinical and radiologic evaluation.MethodsA prospective study of clinical, radiological and urodynamic evaluation in patients with SCT who underwent resection between January 2002–June 2015 and were followed up till January 2016 was conducted.ResultsTotal 57 patients, 42 (73.7%) females and 15 (26.3%) males with 35 (62.4%) following treatment for benign and 22 (38.5%) for malignant disease were included. Twenty-eight of 57 (49.12%) had urological problems. Clinical complaints in 21 (36.8%) patients included stress urinary incontinence-14 (66.7%), enuresis-9 (42.9%), and poor stream or dribbling of urine-6 (28.6%). Eight of 51 patients (15.7%) had abnormal ultrasound findings, which included contracted, trabeculated thick walled bladder (3), bilateral hydronephrosis (3) and significant post void residue (PVR) (6). Seven of 57 underwent micturating cystourethrogram (MCU), 5 had an abnormal report[significant PVR (4), small trabeculated bladder (3), reflux (2) and large capacity bladder (1)]. Urodynamic study was done in 27 patients, 18/27 (66.7%) had abnormalities. Six patients without any clinical or ultrasonographic abnormalities had abnormal UDS. Total 28 (49.12%) had urological comorbidities. Three patients had overactive bladder, five dysfunctional voiding, one underactive bladder and one had giggle incontinence. Children were managed by behaviour therapy and pharmacotherapy.ConclusionUrodynamic evaluation could detect abnormalities in patients who had no urinary complaints or abnormality on ultrasound. The abnormalities have a potential for progressive upper tract damage. Urodynamics should be an integral part of urological surveillance in patients operated for SCT.Type of studyPrognostic study.Level of EvidenceLevel II (Prospective cohort study).     

Child and parental adaptation to pediatric stem cell transplantation

Goals of work  Allogeneic pediatric stem cell transplantation (SCT) is a very intensive treatment with a high mortality and morbidity. The objectives of this study were to assess the (1) self- and proxy-reported health-related quality of life (HRQoL) compared to a norm group, (2) levels of parenting stress compared to a norm group, (3) differences in HRQoL and parenting stress pre- and post-SCT, and (4) effect of child age and parenting stress on self- and proxy-reported HRQoL pre- and post-SCT. Materials and methods  Pre- and on average 10 months post-SCT, 21 children and adolescents and their parent(s) completed questionnaires on HRQoL and the mothers completed a measure of parenting stress. Main results  Post-SCT, home functioning, physical functioning, and total HRQoL scores were lower than the norm group. We found stable HRQoL scores over time with the exception of the domain home functioning, which was rated lower post-SCT than pre-SCT. Parents reported lower HRQoL scores than the children pre- and post-SCT and younger children experienced better HRQoL than older children. Parenting stress was higher post-SCT than pre-SCT and high levels of parenting stress were predictive of poor parental ratings of child HRQoL post-SCT. Conclusions  Ongoing psychosocial assessment post-SCT is necessary to target children with a lowered HRQoL and parents who experience elevated parenting stress who may be in greater need of more supportive care.     

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Objective: The mainstay treatment of esophageal squamous cell carcinoma(ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies.Methods: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor(EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks u...     

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T₂* magnetic resonance (MR) relaxometry is a more accurate alternative for follow‐up in pediatric patients before and after allogenic SCT. Twenty‐three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T₂* relaxometry on a 1.5 T MR‐scanner to estimate liver iron concentrations from the T₂* values (“MR‐Fe”). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR‐Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR‐Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR‐Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.     

Laparoscopic unilateral oophorectomy for ovarian tissue cryopreservation in children

Background/Purpose

Many survivors of childhood cancer will experience premature gonadal insufficiency or infertility as a consequence of their medical treatments. Ovarian tissue cryopreservation (OTC) remains an experimental means of fertility preservation with few reports focused on the surgical technique and postoperative outcomes for OTC in children.

Effect of Sickle Cell Trait on Total Hip Arthroplasty in a Matched Cohort

BackgroundIt is unclear if sickle cell trait (SCT) carrier status conveys an increased risk for poor outcomes following total hip arthroplasty (THA). The purpose of this study is to compare short-term clinical outcomes of THA for patients with SCT vs matched controls.MethodsPatient records were queried from the PearlDiver database using International Classification of Diseases, Ninth and Tenth Revision and Current Procedural Terminology codes. Patients with SCT who underwent THA were matched 1:1 with controls across age, gender, Elixhauser Comorbidity Index, obesity, and US region. Thirty-day and 90-day rates of systemic complications and 1-year and 2-year rates of joint complications were compared with logistic regression.ResultsIn total, 1646 patients were assigned to each cohort. In the 30-day and 90-day postoperative periods, SCT carriers had a higher likelihood of cerebrovascular accident, anemia, acute renal failure, pneumonia, sepsis, deep vein thrombosis, pulmonary embolism, and respiratory failure (all P < .05). SCT carriers exhibited significantly higher risk of periprosthetic joint infection at both 1 (3.5% vs 2.1%; odds ratio [OR] 1.91, 95% confidence interval [CI] 1.22-2.99) and 2 years (3.7% vs 2.6%; OR 1.63, 95% CI 1.07-2.49) postoperatively. Prosthetic loosening was also significantly more likely for SCT carriers within 1 year (1.3% vs 0.3%; OR 4.49, 95% CI 1.75-13.86).ConclusionPatients with SCT exhibited significantly higher risk for systemic complications, periprosthetic joint infection, and prosthetic loosening after THA. Increased perioperative efforts should be made to prevent hypoxia, acidosis, and dehydration, as these states increase red blood cell sickling, which may reduce complication rates and improve outcomes in patients with SCT.