G De Angelis

Response to infliximab is related to disease duration in paediatric Crohn's disease

Background : Infliximab is an effective therapy in adult patients with refractory and fistulizing Crohns disease. Experience in children is still limited.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohns disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non‐erosive reflux disease

Background  Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro‐esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease.

Allogeneic cellular gene therapy in hemoglobinopathies—evaluation of hematopoietic SCT in sickle cell anemia

Many patients with thalassemia have been cured with BMT since the first successful transplant in 1981. Allogeneic stem cell gene therapy is the only treatment option for patients with sickle cell anemia (SCA). A total of 11 patients with a median age of 12 years (range, 2–16), affected by SCA, received hematopoietic SCT from HLA-identical, related donors following a myeloablative-conditioning regimen. Indications for transplantation were vaso-occlusive crisis, acute chest syndrome, avascular bone necrosis, chronic RBC transfusions, or hemorrhagic stroke. All patients had sustained engraftment. One patient became a stable mixed chimera with 25% of donor cells at 4 years after transplantation. One patient died at 1 year after transplantation. The probability of survival, SCA-free survival and TRM at 5 years after transplant were 90, 90 and 10%, respectively. All 10 surviving patients remained free of any SCA-related events after transplantation. In conclusion, these data confirm SCT from a suitable HLA-matched, related donor should become the primary option for curing children with SCA. There is an excellent survival rate and a return to normal life, free of SCA-related events.

Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia.

Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC=68) or reduced (reduced intensity conditioning (RIC)=29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n=60) or in >2nd CR or active disease (advanced phase: n=37). With a median time of 21 days (range 12–38 days), the cumulative incidence (CI) of neutrophil engraftment was 94±3%. The 100-day CI of III–IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9±3% and 12±4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3–5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53±7 vs 24±8% (P=0.006) and 48±7 vs 22±8% (P=0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36±6 vs 28±9%) while the relapse risk was lower for the MAC patients (22±6 vs 45±11%), who showed higher OS (48±7 vs 29±10%) and DFS (43±7 vs 26±10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

Sezary syndrome in relapse after reduced intensity allogeneic transplant successfully treated with donor lymphocyte infusion.

Sezary syndrome in relapse after reduced intensity allogeneic transplant successfully treated with donor lymphocyte infusion

Pre-transplant persistence of minimal residual disease does not contraindicate allogeneic stem cell transplantation for adult patients with acute myeloid leukemia

Despite progress in treatment and supportive therapies, outcome of high-risk adult AML remains dismal with ~ 20% of patients becoming long-term survivors. Since the pretreatment genetics/cytogenetics of AML do not always anticipate the individual outcome, there is a strong rationale to implement laboratory techniques capable of exploring the quality of CR and allowing post-remission therapy to be optimally directed. In this view, minimal residual disease (MRD) assessment promises to be a robust approach. It captures the diversities of the underlying genetic/cytogenetic features of AML and recapitulates other patient heterogeneities regarding drug bioavailability, metabolism and resistance. Multiparametric flow cytometry (MFC) is one of the leading techniques successfully exploited to quantify MRD in AML expressing leukemia-associated immunophenotypes (LAIP). This assay applies to the vast majority of patients after chemotherapy-induced morphologic CR and has been shown to predict the clinical outcome when measured at several time points, potentially prompting prospective treatment adjustments. Recent studies have demonstrated that pretransplant MRD levels negatively affect post-transplant outcome. Years ago, we showed that MRD persistence at the end of consolidation was associated with an unfavorable outcome and that autologous stem cell transplantation (AuSCT) was not able to alter such an unfavorable course. More recently, other authors have extended this observation to either pediatric or adult patients receiving allogeneic stem cell transplantation (ASCT), showing that pretransplant MRD is a major determinant of prognosis, regardless of the occurrence of graft-versus-leukemia (GVL). Nevertheless, whether MRD positivity is an indication or a contraindication to deliver ASCT is still a matter of debate. On the basis of these premises, we analyzed a retrospective series of MRD-positive adults with AML who were submitted to ASCT. Our aim was to evaluate the impact of pretransplant MRD status on overall survival (OS) and DFS. We analyzed 230 consecutive patients achieving CR after the induction cycle of intensive EORTC/GIMEMA protocols and who harbored in their leukemic cells a LAIP suitable for MRD monitoring. The present series represents an extension of a cohort of patients already analyzed for different purposes and reported previously. Following our previous experience, MRD positivity was defined if ⩾ 3.5 × 10 4 (0.035%) residual leukemic cells (RLCs) were detected in the BM upon full hematological recovery after consolidation cycle. According to this definition, 176/230 patients (76.5%) were classified as MRD positive (MRD) and 54/230 (23.5%) as MRD negative (MRD). In the overall series, 84/230 patients (36.5%) received no transplant because of age, poor performance status or insufficient stem cell harvest, 28/230 (12.2%) relapsed before transplant delivery whereas 118/230 (51.3%) underwent ASCT (N= 50) or AuSCT (N= 68) in first CR. For the purpose of the present analysis, we focused on the 81 patients who tested MRD and who were submitted to ASCT (N= 45) or AuSCT (N= 36), respectively. The same analysis was not feasible for MRD patients due to the low numbers in the ASCT group (N= 5), preventing any statistical significance from being demonstrated. The clinico-biological characteristics of the patients are detailed in Table 1. The two groups were balanced regarding white blood cell count (WBCc), ELN risk category, FLT3 and NPM1 mutational status. Karyotypic analysis was available in 77 (95%) out of 81 patients. Intermediate risk category accounted for 78%

An unusual pyloric obstruction: gastroduodenal mucosal intussusception

Gastroduodenal mucosal intussusception was recently observed in a baby girl born with esophageal atresia. After ligation of the tracheoesophageal fistula, a gastrostomy tube was inserted. At 3 months of age an esophagoesophageal anastomosis was performed and oral feeding was begun that resulted in vomiting. An upper gastrointestinal endoscopy confirmed the normal viability of the esophagus and showed intussusception of gastric mucosa into the duodenum. At laparotomy, a wide pylorotomy was done and the intussuscepted mucosa was resected and a pyloroplasty performed. Ten days postoperatively oral feeding was restarted successfully.

Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.