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Article ; Online: Reduced toxicity conditioning and a high CD34

Pandrowala, Ambreen / Sharma, Ajay Narayan / Kakunje, Manasa / Bodhanwala, Minnie / Hiwarkar, Prashant

The journal of allergy and clinical immunology. Global

2023 Volume 2, Issue 3, Page(s) 100106

Abstract: Background: Biallelic mutations in the dedicator of cytokinesis 8 (: Objective: Here we have sought to devise a strategy for reducing the possibility of mixed chimerism without increasing the risk of transplant-related mortality.: Methods: To ... ...

Abstract	Background: Biallelic mutations in the dedicator of cytokinesis 8 ( Objective: Here we have sought to devise a strategy for reducing the possibility of mixed chimerism without increasing the risk of transplant-related mortality. Methods: To balance the risk of transplant-related mortality and mixed chimerism, we used treosulfan-based reduced toxicity conditioning with a high CD34 Results: We are able to report that by using the aforementioned novel strategy, we achieved excellent transplant outcomes in the first cohort of high-risk patients with DOCK8 deficiency from India. Conclusion: High CD34
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article
ISSN	2772-8293
ISSN (online)	2772-8293
DOI	10.1016/j.jacig.2023.100106
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Article ; Online: The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol.

Pandrowala, Ambreen / Khan, Sanna / Kataria, Darshan / Kakunje, Manasa / Mishra, Varsha / Mamtora, Dhruv / Mudaliar, Sangeeta / Bodhanwala, Minnie / Agarwal, Bharat / Hiwarkar, Prashant

Scientific reports

2024 Volume 14, Issue 1, Page(s) 988

Abstract: Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ ... ...

Abstract	Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243-1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.
MeSH term(s)	Humans ; Alemtuzumab/therapeutic use ; Retrospective Studies ; Graft vs Host Disease ; Immunization, Passive ; Cell Size
Chemical Substances	Alemtuzumab (3A189DH42V)
Language	English
Publishing date	2024-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50416-6
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Article ; Online: Periorbital Cellulitis Caused by Herpes Simplex Virus in a Child with Dedicator of Cytokinesis 8 Deficiency.

Pandrowala, Ambreen / Ganatra, Parth / Bodhanwala, Minnie / Sharma, Ajay Narayan / Hiwarkar, Prashant

Indian journal of pediatrics

2022 Volume 89, Issue 7, Page(s) 723

MeSH term(s)	Cellulitis/etiology ; Child ; Cytokinesis ; Eye Diseases ; Humans ; Simplexvirus
Language	English
Publishing date	2022-02-22
Publishing country	India
Document type	Letter
ZDB-ID	218231-2
ISSN	0973-7693 ; 0019-5456
ISSN (online)	0973-7693
ISSN	0019-5456
DOI	10.1007/s12098-022-04108-0
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Zs.A 826: Show issues

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Article ; Online: Somatic CBL mutation presenting as juvenile myelomonocytic leukemia with vasculitis.

Mishra, Varsha / Krishnan, V P / Desai, Mukesh / Manek, Hirva / Pandrowala, Ambreen / Bodhanwala, Minnie / Hiwarkar, Prashant

Pediatric blood & cancer

2023 Volume 70, Issue 6, Page(s) e30252

MeSH term(s)	Humans ; Leukemia, Myelomonocytic, Juvenile/genetics ; Mutation ; Vasculitis ; Proto-Oncogene Proteins c-cbl/genetics
Chemical Substances	Proto-Oncogene Proteins c-cbl (EC 2.3.2.27)
Language	English
Publishing date	2023-02-14
Publishing country	United States
Document type	Letter
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30252
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Article ; Online: The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders

Ambreen Pandrowala / Sanna Khan / Darshan Kataria / Manasa Kakunje / Varsha Mishra / Dhruv Mamtora / Sangeeta Mudaliar / Minnie Bodhanwala / Bharat Agarwal / Prashant Hiwarkar

Scientific Reports, Vol 14, Iss 1, Pp 1-

results of an institutional protocol

2024 Volume 8

Abstract: Abstract Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on ...

Abstract	Abstract Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243–1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article: Narsoplimab for severe transplant-associated thrombotic microangiopathy.

Pandrowala, Ambreen / Ganatra, Parth / Krishnan, V P / Sharma, Ajay Narayan / Chavan, Saroj / Bodhanwala, Minnie / Agarwal, Bharat / Hiwarkar, Prashant

Thrombosis journal

2023 Volume 21, Issue 1, Page(s) 26

Abstract: Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and ... ...

Abstract	Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively. Case presentation: The six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab. Conclusion: Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.
Language	English
Publishing date	2023-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2118392-2
ISSN	1477-9560
ISSN	1477-9560
DOI	10.1186/s12959-023-00464-9
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Article ; Online: Characteristics and Transmission Dynamics of COVID-19 in Healthcare Workers in a Pediatric COVID-Care Hospital in Mumbai.

Pandrowala, Ambreen / Shaikh, Shaheen / Balsekar, Mahesh / Kirolkar, Suverna / Udani, Soonu

Indian pediatrics

2020 Volume 58, Issue 6, Page(s) 568–571

Abstract: Objective: To evaluate if Healthcare workers (HCWs) at the frontline of COVID-19 response in a pediatric hospital are at an increased risk of acquiring SARS-CoV-2.: Methods: The Hospital Infection Control Committee (HICC) and virology testing records ...

Abstract	Objective: To evaluate if Healthcare workers (HCWs) at the frontline of COVID-19 response in a pediatric hospital are at an increased risk of acquiring SARS-CoV-2. Methods: The Hospital Infection Control Committee (HICC) and virology testing records were combined to identify SARS-CoV-2 positive HCWs and study the transmission dynamics of COVID-19 over 6 months. Results: COVID-19 cases in our HCWs cohort rose and declined parallel to community cases. Forty two out of 534 HCWs (8%) were SARS-CoV-2 positive with no fatalities. No clinical staff in the special COVID ward or ICU was positive. Significant proportion of non-clinical staff (30%) were SARS-CoV-2 positive. About 70% of SARS-CoV-2 positive staff had likely community acquisition, with a significant proportion having travelled by public transport or having a contact history with a positive case in the community. Twenty four percent of positive staff were asymptomatic and detected positive on re-joining test. Conclusions: Sustained transmission of SARS-CoV-2 did not occur in our cohort beyond community transmission. Appropriate PPE use, strict and constantly improving infection control measures and testing of both clinical and non-clinical staff were essential methods for restricting transmission amongst HCWs.
Language	English
Publishing date	2020-02-19
Publishing country	India
Document type	Journal Article
ZDB-ID	402594-5
ISSN	0974-7559 ; 0019-6061
ISSN (online)	0974-7559
ISSN	0019-6061
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Zs.A 859: Show issues

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Article ; Online: False-positive blood cultures: The need for follow-up.

Kirolikar, Suverna / Pandrowala, Ambreen / Joshi, Sangeeta / Misra, Ruchira / Mushrif, Sujata

Indian journal of medical microbiology

2020 Volume 38, Issue 3 & 4, Page(s) 469–471

Abstract: The diagnosis of blood-borne infections in immunocompromised patients is a major challenge for the clinical microbiology laboratory. Isolation of bloodborne pathogens in these patients has profound clinical implications, yet is fraught with technical ... ...

Abstract	The diagnosis of blood-borne infections in immunocompromised patients is a major challenge for the clinical microbiology laboratory. Isolation of bloodborne pathogens in these patients has profound clinical implications, yet is fraught with technical problems, including the presence of unusual and difficult to isolate pathogens. Coupled with this is the problem of false-positive blood culture signals from automated blood culture systems which further delays the definitive diagnosis. Here, we present a case of an 8-year-old boy with Ph +ve acute lymphoblastic leukaemia who has repeated 'false positive' blood cultures and later grew an uncommon organism.
MeSH term(s)	Amikacin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Azithromycin/therapeutic use ; Blood Culture/standards ; Blood-Borne Infections/blood ; Blood-Borne Infections/diagnosis ; Child ; Clofazimine/therapeutic use ; Diagnosis, Differential ; False Positive Reactions ; Humans ; Immunocompromised Host ; Levofloxacin/therapeutic use ; Male ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/drug therapy ; Mycobacterium abscessus/drug effects ; Mycobacterium abscessus/isolation & purification ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
Chemical Substances	Anti-Bacterial Agents ; Levofloxacin (6GNT3Y5LMF) ; Azithromycin (83905-01-5) ; Amikacin (84319SGC3C) ; Clofazimine (D959AE5USF)
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1038798-5
ISSN	1998-3646 ; 0255-0857
ISSN (online)	1998-3646
ISSN	0255-0857
DOI	10.4103/ijmm.IJMM_20_402
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Article ; Online: SLGT2 Inhibitor Rescues Myelopoiesis in G6PC3 Deficiency.

Hiwarkar, Prashant / Bargir, Umair / Pandrowala, Ambreen / Bodhanwala, Minnie / Thakker, Naresh / Taur, Prasad / Madkaikar, Manisha / Desai, Mukesh

Journal of clinical immunology

2022 Volume 42, Issue 8, Page(s) 1653–1659

Abstract: The energy metabolism of myeloid cells depends primarily on glycolysis. 1,5-Anhydroglucitol (1,5AG), a natural monosaccharide, is erroneously phosphorylated by glucose-phosphorylating enzymes to produce 1,5-anhydroglucitol-6-phosphate (1,5AG6P), a ... ...

Abstract	The energy metabolism of myeloid cells depends primarily on glycolysis. 1,5-Anhydroglucitol (1,5AG), a natural monosaccharide, is erroneously phosphorylated by glucose-phosphorylating enzymes to produce 1,5-anhydroglucitol-6-phosphate (1,5AG6P), a powerful inhibitor of hexokinases. The endoplasmic reticulum transporter (SLC37A4/G6PT) and the phosphatase G6PC3 cooperate to dephosphorylate 1,5AG6P. Failure to eliminate 1,5AG6P is the mechanism of neutrophil dysfunction and death in G6PC3-deficient mice. Sodium glucose cotransporter 2 (SLGT2) inhibitor reduces 1,5AG level in the blood and restores the neutrophil count in G6PC3-deficient mice. In the investigator-initiated study, a 30-year-old G6PC3-deficient woman with recurrent infections, distressing gastrointestinal symptoms, and multi-lineage cytopenia was treated with an SLGT2-inhibitor. A significant increase in all the hematopoietic cell lineages and substantial improvement in the quality of life was observed.
MeSH term(s)	Animals ; Humans ; Mice ; Antiporters ; Glucose-6-Phosphatase/genetics ; Glucose-6-Phosphatase/metabolism ; Monosaccharide Transport Proteins/genetics ; Myelopoiesis ; Neutropenia ; Phosphoric Monoester Hydrolases/metabolism ; Quality of Life ; Glycogen Storage Disease Type I/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Female ; Adult
Chemical Substances	Antiporters ; G6PC3 protein, human (EC 3.1.3.9.) ; Glucose-6-Phosphatase (EC 3.1.3.9) ; Monosaccharide Transport Proteins ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; SLC37A4 protein, human ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2022-07-15
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-022-01323-4
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Article ; Online: X-Linked Hyper IgM Syndrome Presenting with Recurrent Tuberculosis-a Case Report.

Krishnan, V P / Taur, Prasad / Pandrowala, Ambreen / Madkaikar, Manisha / Desai, Mukesh

Journal of clinical immunology

2020 Volume 40, Issue 3, Page(s) 531–533

Abstract: The hyper IgM syndromes are a group of rare primary immunodeficiency disorders. Currently 6 classes of HIGM are described. X-linked HIGM is also called the type 1 HIGM is the commonest variant in which children present in early infancy with features of ... ...

Abstract	The hyper IgM syndromes are a group of rare primary immunodeficiency disorders. Currently 6 classes of HIGM are described. X-linked HIGM is also called the type 1 HIGM is the commonest variant in which children present in early infancy with features of combined immunodeficiency. Tuberculosis is a very rare presentation as a presenting symptom in HIGM. Here, we describe a child with XHIGM with recurrent tuberculosis.
MeSH term(s)	Child, Preschool ; Humans ; Hyper-IgM Immunodeficiency Syndrome, Type 1/diagnosis ; Image-Guided Biopsy ; Infant ; Male ; Recurrence ; Respiratory Insufficiency ; Skin Tests ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis ; X-Linked Combined Immunodeficiency Diseases/diagnosis
Language	English
Publishing date	2020-01-22
Publishing country	Netherlands
Document type	Case Reports ; Letter
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-020-00747-0
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