Fatal Severe Cytokine Release Syndrome Post-haploidentical Stem Cell Transplant With Post-transplant Cyclophosphamide in an Infant With Severe Combined Immunodeficiency and Disseminated Bacille Calmette-Guérin Infection.

INTRODUCTION: Severe Combined Immunodeficiency (SCID) is a primary immunodeficiency disorder characterized by absent or dysfunctional T lymphocytes, leading to defective cellular and humoral immunity requiring urgent hematopoietic stem cell transplantation (HSCT). We report a case of SCID with disseminated Bacille Calmette-Guérin (BCG) infection who developed cytokine release syndrome (CRS) and possible Immune reconstitution inflammatory syndrome (IRIS) after Haploidentical HSCT with post-transplant cyclophosphamide. METHODS: Data were retrospectively retrieved from electronic medical records. RESULT: A 5-month-old male infant was referred with fever, cough, and generalized maculopapular rash for 15 days, and had pallor without hepatosplenomegaly or lymphadenopathy. He had a history of previous male sibling death at 6 months of age due to pneumonia. Investigations: hemoglobin: 4.7 g/dL, TLC-6.37×103/uL, absolute lymphocytes: 0.98×103/uL, platelets: 319×103/uL, bilateral patchy opacities in both lung fields, and low immunoglobulin levels. Lymphocyte subset analysis revealed T-, B+, NK- SCID. Genetic analysis showed a hemizygous mutation in IL2RG (c.314A>G). The child received intravenous (IV) antibiotics, antifungal, antitubercular drugs, irradiated blood products, and IV immunoglobulins. Urgent haploidentical HSCT from the mother was planned. Conditioning was Fludarabine-40 mg/m2/d for 4 days, cyclophosphamide: 14.5 mg/kg/d for 2 days. He received peripheral blood hematopoietic stem cells with CD34- 15×106 cells/kg and CD3- 805×106 cells/kg. Within 2 hours of stem cell infusion, he developed respiratory distress, fever, shock, and flaring of rash. Methylprednisolone was started in view of CRS. On day+2, he had sudden desaturation and bradycardia needing mechanical ventilation and inotropes. His inflammatory markers were elevated (Ferritin: 3640 ng/mL, IL-6:5000 pg/mL, CRP:255 mg/L). In view of high-grade CRS, he received an injection of tocilizumab 8 mg/kg on day +2 and day +4. He received post-transplant cyclophosphamide 5 mg/kg on day +3. The endotracheal secretion GeneXpert was positive for Mycobacterium supporting the diagnosis of disseminated tuberculosis. Our patient had disseminated BCG infection which could also be contributory in the initiation of IRIS as the mother was immunized with the BCG vaccine in childhood so she must be having cytotoxic T cells specific for BCG, which were transferred to the infant with peripheral blood stem cell product. He succumbed to severe acute respiratory distress syndrome and multiorgan dysfunction on day +5 post-transplant. CONCLUSIONS: In haploidentical HSCT of SCID, post-transplant course can be complicated by CRS and IRIS as these patients are inefficient in mounting any response to infused donor lymphocytes resulting in their unregulated growth.

Bacillus cereus infection in pediatric oncology patients: A case report and review of literature.

INTRODUCTION: Bacillus Cereus infection can be life-threatening in immunocompromised patients. We report here a case of Bacillus Cereus septicemia in a child with relapsed acute lymphoblastic leukemia (ALL) and present review of literature. METHODS: We collected clinical, laboratory and outcome data of our patient with relapsed ALL and Bacillus Cereus infection. We reviewed literature for Bacillus Cereus infection in pediatric oncology patients by searching MED-LINE/PubMed/Google/Google Scholar/Cochrane and summarized the data obtained. Various risk factors like presence of gastrointestinal or central nervous system (CNS) symptoms, neutropenia, central venous catheter in-situ, corticosteroids use, intrathecal chemotherapy and outcomes were analyzed using Fisher Exact Chi Square test. RESULTS: A 15-years-old boy with relapsed ALL on induction chemotherapy presented with giddiness and difficulty in breathing. He had an episode of hematemesis followed by fainting at home. He had refractory shock which did not respond to fluid boluses, inotropes and hydrocortisone. He had severe metabolic acidosis with high lactate and ammonia and died within 36-hours of onset of symptoms. His blood culture was positive for Bacillus Cereus. We came across 36 published cases of Bacillus Cereus in children with cancer including present case. Of these, 28 had acute leukemia and rest 8 had other cancers. CNS symptoms were present in 13 patients. Overall mortality was 25%. Patients with multisystem involvement had significantly higher mortality compared to those having localized disease (p-value 0.033). CONCLUSION: In pediatric oncology patients on chemotherapy, cultures positive for Bacillus Cereus should be considered significant. Mortality is higher in those with multisystem involvement.

Dengue virus transmission from donor to recipient during haploidentical stem cell transplantation.

Dengue fever is endemic in tropical and subtropical countries. Dengue virus transmission through hematopoietic stem cells is very rare and just two such cases have been reported previously. We report here only third case of dengue virus transmission in a 2-year-old child with thalassemia major who underwent hematopoietic stem cell transplant (HSCT) from a haploidentical related donor. One week after HSCT, the recipient developed fever, pancytopenia and signs of capillary leak. On day 10, his dengue NS1 antigen test was positive which confirmed diagnosis of dengue fever. Donor also had fever few days prior to stem cell donation which was later diagnosed to be due to dengue fever. Child had a severe clinical course of dengue leading to primary graft failure. However, he had autologous recovery of his own bone marrow and is alive and well on day+200 post HSCT. Our report highlights the transmission of dengue virus from donor to recipient through hematopoietic stem cell graft although rare but possible. We suggest that in tropical and subtropical countries where dengue is endemic, hematopoietic stem cell donors should be screened for it.

Linear angular momentum multiplexing-conceptualization and experimental evaluation with antenna arrays.

Linear angular momentum multiplexing is a new method for providing highly spectrally efficient short-range communication between a transmitter and receiver, where one may move at speed transverse to the propagation. Such applications include rail, vehicle and hyperloop transport systems communicating with fixed infrastructure on the ground. This paper describes how the scientific concept of linear angular momentum multiplexing evolves from orbital angular momentum multiplexing. The essential parameters for implementing this concept are a long array at least at one of the ends of the link; antenna element radiation characteristics and the array element spacing relative to the propagation distance. These parameters are also backed by short-range measurements carried out at 2.4 GHz used to model the Rice fading channel and determine resilience to multipath fading.