Primary renal leukaemia in a young adult male as an extramedullary presentation of T cell acute lymphoblastic leukaemia.

Primary renal involvement by T lymphoblasts is rare among adults with T acute lymphoblastic leukaemia. We report a 28-year-old man presenting with acute renal failure due to infiltration by T lymphoblasts and his response to paediatric-inspired modified BFM-90 protocol. The patient achieved an initial complete remission (CR) but developed central nervous system relapse. He achieved CR2 with cranial irradiation and intrathecal chemotherapy. He underwent a haploidentical transplant in CR2 and remains in remission post-transplant day 330. An early kidney biopsy helped confirm the diagnosis. Such presentations remain responsive to modified BFM-90. An early allotransplant in CR2 remains the standard of care.

Chronic enteropathy-related malabsorption syndrome in an adult with common variable immunodeficiency and symptomatic norovirus infection of the gut.

Common variable immunodeficiency (CVID) causes a chronic debilitating syndrome in affected patients and often leads to high morbidity and mortality. Among its several presentations, chronic enteropathy leading to malabsorption syndrome continues to offer a major diagnostic dilemma. Lately, higher testing for norovirus infection in patients with CVID enteropathy has correlated its presence to chronic diarrhoeas, severe villous atrophy and malabsorption syndromes. There have been no such reports of its clinical and histopathological manifestations in CVID from India. Here, we demonstrate the significance of testing for norovirus in the gut with multiplex PCRs in an adult patient with a chronic undiagnosed CVID enteropathy and its response to monthly intravenous immunoglobulin (IVIG) therapy. Our patient responded after three cycles of monthly IVIG with a complete clinical recovery of his bowel functions, leading to a significant improvement in his quality of life and performance status.

Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A).

Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in the AK1 gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in the AK1 gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger's sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation in AK1 gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population.

Antibiotic lock therapy for salvage of tunneled central venous catheters with catheter colonization and catheter-related bloodstream infection.

Central venous catheters (CVCs) represent a significant source of infection in patients undergoing hematopoietic stem cell transplantation and can add to the cost of care, morbidity, and mortality. Organisms forming biofilms on the inner surface of catheters require a much higher local antibiotic concentration to clear the pathogen growth. Antibiotic lock therapy (ALT) represents one such strategy to achieve such high intraluminal concentrations of antibiotics and can facilitate catheter salvage. Patients with catheter colonization (CC) or hemodynamically stable catheter-related bloodstream infection (CRBSI) received ALT per institutional policy. We analyzed the incidence of CC and CRBSI and salvage rate of tunneled CVCs (Hickman) with ALT in patients undergoing hematopoietic stem cell transplant in this retrospective study. Catheter colonization was noted in 9.8% and CRBSI in 10.7% patients. Gram-negative bacilli (GNB) accounted for 45% and 83% of isolates in CC and CRBSI, respectively. In patients with CRBSI, the rate of catheter salvage with the use of ALT in addition to systemic antibiotics was 86% compared to 55% in patients with systemic antibiotics use only (P = 0.06). There was no CRBSI related mortality, and no increase in resistant strains was noted at subsequent CRBSI. In conclusion, ALT represents an important strategy for catheter salvage, especially for gram-negative infections, in a carefully selected patient population.

Adult Acute Lymphoblastic Leukemia: Limitations of Intensification of Therapy in a Developing Country.

Purpose Limited data exist on intensifying chemotherapy regimens in the treatment of adult acute lymphoblastic leukemia (ALL) outside the setting of a clinical trial. Materials and Methods Retrospectively, data from 507 consecutive adults (age ≥ 15 years) with a diagnosis of ALL treated at our center were analyzed. Standard-risk (SR) patients were offered treatment with a modified German Multicenter ALL (GMALL) regimen, whereas high-risk (HR) patients were offered intensification of therapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD). Because of resource constraints, a proportion of HR patients opted to receive the same treatment regimen as used for SR patients. Results There were 344 SR patients (67.8%) and 163 HR patients (32.2%) at diagnosis. Among the HR patients, 53 (32.5%) opted to receive intensification with the HCVAD regimen. The SR cohort showed a superior 5-year event-free survival rate compared with the HR cohort (47.3% v 23.6%, respectively; P < .001). Within the HR subgroup, there was no statistically significant difference in overall survival or event-free survival between patients who received the modified GMALL regimen (n = 59) and patients who received HCVAD (n = 53). Conclusion Intensified therapy in the HR subset was associated with a significant increase in early treatment-related mortality and cost of treatment. A modified GMALL regimen was found to be cost-effective with clinical outcomes comparable to those achieved with more intensive regimens.

Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

OBJECTIVE/BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. METHODS: We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. RESULTS: The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. CONCLUSION: Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN.

Surgical procedures in patients with Glanzmann's thrombasthenia: case series and literature review.

Glanzmann's thrombasthenia is a rare platelet function disorder with an autosomal recessive pattern of inheritance. Achieving haemostasis in such patients who undergo surgical procedures always poses a significant challenge. Herein we report six cases of Glanzmann's thrombasthenia, who underwent nine surgeries under the cover of platelet-rich concentrates with or without recombinant activated factor VII . Of these, five were major surgeries such as thyroidectomy, laparotomy, Hartmann's procedure, reversal of Hartmann's procedure and a complete dental extraction. All five procedures were successfully done without any major bleeding. The major cost incurred in these procedures is due to the large number of blood products used and recombinant activated factor VII if used.

Acute myeloid leukaemia: challenges and real world data from India.

The management of acute myeloid leukaemia (AML) in India remains a challenge. In a two-year prospective study at our centre there were 380 newly diagnosed AML (excluding acute promyelocytic leukaemia, AML-M3) patients. The median age of newly diagnosed patients was 40 years (range: 1-79; 12.3% were ≤ 15 years, 16.3% were ≥ 60 years old) and there were 244 (64.2%) males. The median duration of symptoms prior to first presentation at our hospital was 4 weeks (range: 1-52). The median distance from home to hospital was 580 km (range: 6-3200 km). 109 (29%) opted for standard of care and were admitted for induction chemotherapy. Of the 271 that did not take treatment the major reason was lack of financial resources in 219 (81%). There were 27 (24.7%) inductions deaths and of these, 12 (44.5%) were due to multidrug-resistant gram-negative bacilli and 12 (44.5%) showed evidence of a fungal infection. The overall survival at 1 year was 70.4% ± 10.7%, 55.6% ± 6.8% and 42.4% ± 15.6% in patients aged ≤ 15 years, 15 - 60 years and ≥ 60 years, respectively. In conclusion, the biggest constraint is the cost of treatment and the absence of a health security net to treat all patients with this diagnosis.