CTLA4Ig in an Extended Schedule along with Sirolimus Improves Outcome with a Distinct Pattern of Immune Reconstitution Following Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation for Hemoglobinopathies.

The major hindrances to the success of a haploidentical hematopoietic cell transplantation for hemoglobinopathies are graft failure, early post-transplant hemophagocytic syndrome (PTHPS), and graft-versus-host disease (GVHD). Following the successful incorporation of CTLA4Ig (abatacept) in post-transplantation cyclophosphamide-based haploidentical transplantation, we piloted this approach in 10 patients (aged 3 to 19 years), with thalassemia major (TM, n=5) and sickle cell disease (n = 5). Pretransplant immunosuppressive therapy (pTIST) was administered for 10 weeks. Conditioning was myeloablative. CTLA4Ig was administered every 2 weeks during pTIST and on days -1, +5, +20, and +35 and every 4 weeks thereafter for 6 months, along with sirolimus. A short course of low-dose dexamethasone was given from day +6 for 14 days. Nine patients engrafted at a median of 15 days, with 1 patient with TM dying of sepsis on day +19. None of the patients developed acute or chronic GVHD. All 9 patients are alive and disease free at a median follow-up of 28 months. Only 4 patients had cytomegalovirus reactivation. The pattern of immune reconstitution showed a prompt and sustained recovery of T cell subsets with memory phenotype, along with early and sustained increase of Tregs and NKG2C+ natural killer (NK) cells. This novel approach, targeting CD80 and CD86 on monocytes/macrophages, promoted engraftment and limited early-onset PTHPS and graft failure. The lack of GVHD and serious infections with this approach reflects an early recovery of Tregs, memory T cells, and persistence of NKG2C+ NK cells.

Influence of New FIGO 2018 Staging on Treatment Outcomes in Early-Stage Cervical Cancer: A Single-Center Study.

Satinder KaurPurpose The aim of this article was to study survival outcomes of early-stage cervical cancer patients and impact on survival after restaging them as per International Federation of Gynecology and Obstetrics (FIGO) 2018. Materials and Methods A retrospective study was conducted from June 1, 2013 to May 31, 2018 in a tertiary care hospital in North India. One-hundred patients of early-stage cervical cancer (as per FIGO 2009 staging) who had been treated by surgery followed by risk based tailored adjuvant therapy in our hospital were evaluated. The clinicopathological features and survival outcomes of these patients were analyzed. These patients were then restaged as per new FIGO 2018 staging and survival outcomes between two FIGO classifications were compared. Results The median age of the study population was 52.5 years with median follow-up of 62.1 months. Ninety percent of our patients had more than 2 years follow-up and 59% had more than 5 years follow-up. The overall survival and relapse-free survival were 87.5 and 91.4%, respectively. The study population was then reclassified according to new FIGO 2018 staging. It was seen that the patients with stage IB1and IB2 cervical cancer had overall survival of 91.1 and 90%, respectively. The overall survival of stage IB3 was 80% and the survival of stage IIIC1 was only 60%. Conclusion The new FIGO 2018 classification has a significant effect on survival outcome and in prognostication of patients with cervical cancer.

Extensive titanium mesh invasive cranial fibrous dysplasia.

BACKGROUND: Craniofacial fibrous dysplasia (FD) is a benign lesion. It presents as bony swelling. Even after complete excision, it has a tendency to recur due to some residual lesion in normal bone. Recurrence at same site is common, but it recurs in bone. We are reporting a rare case of recurrent FD engulfing titanium mesh. CASE DESCRIPTION: A 22-year-old girl, who underwent frontal FD excision and reconstruction using titanium mesh surgery 2 years back, came with complaint of progressive bony swelling at same site for 1 year. CT head confirmed bony lesion involving mesh, frontal air sinus. She underwent complete excision of lesion and cranioplasty using bony cement. Biopsy confirmed recurrence of FD and invasion of titanium mesh. CONCLUSION: Recurrence of FD, involving cranioplasty titanium mesh, is extremely rare. It suggests local invasiveness of lesion. Recurrence can be prevented by excision of lesion with free bony margins.

T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia.

We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0.04). Chronic GVHD (12.5% vs 56%, p=0.02) and CMV reactivation (30% vs 80%, p=0.03) were also reduced in the COSBL group. T and NK cell subset analysis revealed higher CD56brightCD16- NK cells in the CONTROL group (p=0.004), but similar CD56dimCD16+ NK cells in both groups at day+30. Tregs (CD4+CD25+CD127dim/- FoxP3+) were markedly higher in the COSBL group at day+30 (8.4% vs 1.1%) and the trend was maintained through day+90 (p<0.01). The GVHD and Disease-free survival at one year in the COSBL group was 80% vs. 30% in the CONTROL group (p=0.05). Our preliminary findings suggest that COSBL in combination with PTCy and sirolimus might augment transplantation tolerance in children with SAA, probably due to synergistic effect on early recovery of Tregs.

T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation.

The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, developed hyperacute SR-GVHD. We report on the outcome of two different regimens for treatment of SR-GVHD on the outcome of these patients. Five patients were treated in Regimen A consisting of anti-thymocyte globulin, Etanercept and Basiliximab. The next 5 patients were treated combining T cell costimulation blockade with Abatacept along with Etanercept and Basiliximab. The overall response at days 29 and 56 were 40% and 0% with Regimen A and100% and 40% with Regimen B. The major cause of treatment failure was progression of GVHD and opportunistic infections. Two of the patients achieving a complete remission on Regimen B are long term disease free survivors off immunosuppression. Our study demonstrates the dismal outcome of early onset SR-GVHD in children following T replete haploidentical transplantation. However, the combination of Abatacept with anticytokine agents seems to produce encouraging early response and might warrant further investigation.

Oro-facial swelling: ultrasonographic aid in the diagnosis.

Oro-facial swellings are frequently encountered in clinical practice. The aim of this report is to unveil the uncommon manifestation of a common clinical problem and the help of ultrasonographic imaging in the diagnosis.

Biliary ascariasis: radiological clue to diagnosis.

Ascariasis is caused by Ascaris lumbricoides. It is the most common helminthic infection seen worldwide. Ascariasis is an endemic disease in our country. This is due to the prevailing poor sanitary conditions and low level of education. Biliary ascariasis is an uncommon cause of obstructive jaundice. We report a case of biliary ascariasis in a young labourer who presented with acute abdominal pain.

Multiple Bony Metastatic Lesions and Evaluation of Primary: Case Records of a Cancer Research Centre.

During 2012-13, we diagnosed 4 patients with extensive skeletal tuberculosis (TB) who were referred to us as cases of bony metastasis with unknown primary. Radiological investigations done outside favoured a diagnosis of disseminated malignancy. Positron emission tomography/computed tomography (PET/CT) scan performed in our institute for localization of primary lesion also suggested metastatic disease. There was no evidence of malignancy on histo-pathological examination (HPE) of the involved sites. The diagnosis of TB was established on characteristics HPE. This article highlights the diagnostic dilemma of PET/CT in cases of TB versus malignancy and the importance of HPE for reaching an accurate diagnosis.

Lipid peroxidation in bronchial asthma.

OBJECTIVE: To study the levels of free oxygen redicals in children with bronchial asthma during an attack and symptom free interval. METHODS: Serum Malondiadehyde (MDA) levels were studied in 25 children between the age of 6 years-14 years who presented with an acute attack of bronchial asthma. In each patient, serum MDA levels were measured at the time of admission, 24-48 hours after good response to treatment and after a symptom free interval of 3 weeks. Results were compared with control group. RESULTS: In study group serum MDA levels were highest at the time of admission, which decreased significantly at 24-48 hours with treatment. After a 3 weeks symptom free interval serum MDA levels had decreased further but were still higher than healthy control group. CONCLUSION: Lipid peroxidation is increased in bronchial asthma during an acute attack and symptom free period.

Prevalence of Pseudomonas aeruginosa in post-operative wound infection in a referral hospital in Haryana, India.

BACKGROUND: The objective of our study was to determine the prevalence of Pseudomonas aeruginosa in the isolates of postoperative wound and its susceptibility pattern to commonly used antibiotics. MATERIALS AND METHODS: During a 2-year period, specimens were received as postoperative wound swabs in Microbiology Laboratory, Maharaja Agrasen Medical College, Agroha (Hisar), Haryana, India. RESULT: Of the 300 bacterial isolates, 89 (29.6%) were P. aeruginosa, followed by Escherichia coli (61, 20.3%), Klebsiella spp. (50, 16.6%), Staphylococcus aureus (43, 14.3%), Proteus spp. (19, 6.3%), Acinetobacter spp. (9, 3.0%), and Citrobacter freundii (2, 0.6%). There was no growth in 27 (9.0%) specimens. CONCLUSION: P. aeruginosa isolation was higher in male patients and most common in the age group of 21-40 years. The susceptibility pattern showed the organism to be most commonly susceptible to imipenem, followed by meropenem, cefoperazone/sulbactam, ticarcillin/clavulanate, and amikacin.