Shalini Shenoy

Publications (11)38.92 Total impact

• Article: Outcomes of allogeneic hematopoietic cell transplant in patients with dyskeratosis congenita.

  Shahinaz M Gadalla, Carmem Sales-Bonfim, Jeanette Carreras, Blanche P Alter, Joseph H Antin, Mouhab Ayas, Prasad Bodhi, Jeffrey Davis, Stella M Davies, Eric Deconinck, [......], Reuven Or, Carol M Richman, Philip S Rosenberg, Jose Sanchez de Toledo Codina, Shalini Shenoy, Gerard Socié, Jakub Tolar, Kirsten M Williams, Mary Eapen, Sharon A Savage
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  ABSTRACT: We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita transplanted between 1981 and 2009. The median age at transplantation was 13 years (range 2 - 35). Approximately 50% of transplants were from related donors. Bone marrow was the predominant source of stem cells (n=24/34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II-IV acute GVHD and the 3-year probability of chronic GVHD were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplantation due to graft failure (n=6) or other transplant-related complications; 9 of these patients had been transplanted from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years from transplantation, 4 of these were attributed to pulmonary failure. Transplant-regimen intensity and transplants from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing non-radiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2013; · 3.15 Impact Factor
• Article: Successful treatment of recurrent hyperhemolysis syndrome with immunosuppression and plasma-to-red blood cell exchange transfusion.

  Erik J Uhlmann, Shalini Shenoy, Lawrence T Goodnough
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  ABSTRACT: BACKGROUND: Hyperhemolysis syndrome is a serious transfusion reaction mostly reported in association with sickle cell disease, characterized by destruction of both donor and host red blood cells (RBCs) by an unknown mechanism. CASE REPORT: A 21-year-old man with sickle cell disease and multiple prior transfusions received two phenotype-matched, compatible RBC units during a brief admission for pain crisis. He developed rapid-onset progressive anemia and hemoglobinuria. Methylprednisolone, erythropoietin, and rituximab were administered. Fifteen days posttransfusion the hemoglobin (Hb) concentration decreased to 3.1 g/dL, with evidence of severe congestive heart failure. No new antibodies were identified. It was felt that his heart failure would not improve without increasing oxygen-carrying capacity. A combination of volume overload, anemia, and hemolysis prompted a novel isovolemic procedure to increase Hb level without removing his own RBCs or causing fluid overload. A cell separator was used operating on the plasma-exchange program, with three cross-match-compatible, washed RBC units as the replacement fluid. After the procedure, there was no evidence of hemolysis. Over the following 6 days, the congestive heart failure resolved, the Hb concentration increased to 7.5 g/dL, and the patient fully recovered. He had a similar event 3 years previously. CONCLUSIONS: Plasma-to-RBC replacement may be beneficial for selected patients with life-threatening anemia. This intervention provides immediate improvement in oxygen-carrying capacity, conserving the patient's own RBCs, while avoiding fluid overload. Although blood transfusion may precipitate further hemolysis, this case report describes successful plasma-to-RBC exchange transfusion with concurrent supportive care to offset hemolysis, including corticosteroid, intravenous immunoglobulin, and rituximab.
  Transfusion 05/2013; · 3.22 Impact Factor
• Source

  Available from: Shashikant Kulkarni

  Article: Acquired monosomy 7 myelodysplastic syndrome in a child with clinical features suggestive of dyskeratosis congenita and IMAGe association

  Sharon Mcdonald, David B Wilson, Elena Pumbo, Shashikant Kulkarni, Philip J Mason, Tobias Else, Monica Bessler, Thomas Ferkol, Shalini Shenoy
  Pediatr Blood Cancer. 01/2010; 54:154-157.
• Article: Acquired monosomy 7 myelodysplastic syndrome in a child with clinical features suggestive of dyskeratosis congenita and IMAGe association.

  Sharon McDonald, David B Wilson, Elena Pumbo, Shashikant Kulkarni, Philip J Mason, Tobias Else, Monica Bessler, Thomas Ferkol, Shalini Shenoy
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  ABSTRACT: We describe a case of acquired monosomy 7 myelodysplastic syndrome (MDS) in a boy with congenital adrenocortical insufficiency, genital anomalies, growth delay, skin hyperpigmentation, and chronic lung disease. Some of his clinical manifestations were suggestive of dyskeratosis congenita (DC), while other features resembled IMAGe association. DC has been linked to mutations in telomere maintenance genes. The genetic basis of IMAGe association is unknown, although mice harboring a mutation in a telomere maintenance gene, Tpp1, have adrenal hypoplasia congenita. We considered the possibility that this patient has a defect in telomere function resulting in features of both DC and IMAGe association.
  Pediatric Blood & Cancer 09/2009; 54(1):154-7. · 1.89 Impact Factor
• Article: Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias.

  Aarati Rao, Michael Kelly, Mark Musselman, Jagadeesh Ramadas, David Wilson, William Grossman, Shalini Shenoy
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  ABSTRACT: Autoimmune hematologic cytopenias in children often require therapeutic intervention. We report a prospective pediatric multicenter trial of rituximab for refractory or steroid-dependent patients. Four doses of rituximab (375 mg/m(2)/dose) were administered weekly. Patients without response after three doses were offered dose escalation to 750 mg/m(2)/dose/week x 3. Safety, efficacy, and immunologic tests were evaluated after therapy. Twenty-nine of 30 children (2-18 years) with thrombocytopenia (21), hemolytic anemia (6), Evans syndrome (2), and neutropenia (1) received at least four doses of rituximab. One developed anaphylaxis with the first dose. One patient was subsequently diagnosed with monosomy 7 myelodysplasia. Of 28 remaining patients, 9 received dose escalation. Responders discontinued other therapy following rituximab. The overall response rate was 72% with median follow-up of 18 months. Complete remission was observed in 14 (50%); all received four doses of rituximab. Partial remission (PR) was observed in six (22%); five had received dose escalation. Of four relapses, 4-24 months after therapy, two were retreated with rituximab and achieved second remission. No major infections were encountered. Circulating B-cells were depleted by 1 month and normalized by 1 year. IgM, Ig A, and IgG levels decreased 6, 9, and 12 months after therapy, respectively, but remained near normal range. Tetanus toxoid antibody titers remained detectable. Rituximab was well tolerated, and induced sustained remissions in children with refractory immune cytopenias. Dose escalation and re-treatment after relapse elicited additional responses. Rituximab therapy should be considered prior to potential interventions with higher toxicity.
  Pediatric Blood & Cancer 05/2008; 50(4):822-5. · 1.89 Impact Factor
• Article: Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias

  Aarati Rao MD, PhD Michael Kelly MD, Mark Musselman MD, Jagadeesh Ramadas MD, PhD David Wilson MD, PhD William Grossman MD, Shalini Shenoy MD, Aarati Rao, Michael Kelly, Mark Musselman, Jagadeesh Ramadas, David Wilson, William Grossman, Shalini Shenoy
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  ABSTRACT: Background Autoimmune hematologic cytopenias in children often require therapeutic intervention. We report a prospective pediatric multicenter trial of rituximab for refractory or steroid-dependent patients.Methods Four doses of rituximab (375 mg/m2/dose) were administered weekly. Patients without response after three doses were offered dose escalation to 750 mg/m2/dose/week × 3. Safety, efficacy, and immunologic tests were evaluated after therapy.ResultsTwenty-nine of 30 children (2–18 years) with thrombocytopenia (21), hemolytic anemia (6), Evans syndrome (2), and neutropenia (1) received at least four doses of rituximab. One developed anaphylaxis with the first dose. One patient was subsequently diagnosed with monosomy 7 myelodysplasia. Of 28 remaining patients, 9 received dose escalation. Responders discontinued other therapy following rituximab. The overall response rate was 72% with median follow-up of 18 months. Complete remission was observed in 14 (50%); all received four doses of rituximab. Partial remission (PR) was observed in six (22%); five had received dose escalation. Of four relapses, 4–24 months after therapy, two were retreated with rituximab and achieved second remission. No major infections were encountered. Circulating B-cells were depleted by 1 month and normalized by 1 year. IgM, Ig A, and IgG levels decreased 6, 9, and 12 months after therapy, respectively, but remained near normal range. Tetanus toxoid antibody titers remained detectable.Conclusions Rituximab was well tolerated, and induced sustained remissions in children with refractory immune cytopenias. Dose escalation and re-treatment after relapse elicited additional responses. Rituximab therapy should be considered prior to potential interventions with higher toxicity. Pediatr Blood Cancer 2008;50:822–825. © 2007 Wiley-Liss, Inc.
  Pediatric Blood & Cancer 03/2008; 50(4):822 - 825. · 1.89 Impact Factor
• Article: Stem cell transplantation in genetically linked regulatory T-cell disorders.

  Shalini Shenoy
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  ABSTRACT: T-regulatory disorders are a heterogenous group characterized by autoimmune and allergic manifestations of varying onset, severity, and progression. The advent of sophisticated molecular and immunologic diagnostic techniques has resulted in accurate elucidation of etiopathogenesis of many immunoregulatory disorders previously clubbed under the autoimmune umbrella. The severity of presentation and progression, early morbidity and mortality, poor quality of life, and frequent refractoriness to immunosuppressive therapy has prompted studies of stem cell transplantation in many immunoregulatory disorders. The benefits of autologous or allogeneic transplantation are related to either suppression and reprogramming of the immune system (autologous transplant) or replacement of missing elements of immune regulation (allogeneic transplants). Transplant methods have steadily improved through a series of studies and trials to have the benefits of this approach outweigh the risks of procedure-related toxicities. This article summarizes the current status and the future goals of stem cell transplantation for T-cell immunoregulatory disorders and reviews advances in disease detection, targeted transplant strategies and novel approaches, and the pros and cons of transplant in this field.
  Chemical immunology and allergy 02/2008; 94:211-9.
• Article: A randomized double-blind trial of hydroxychloroquine for the prevention of chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.

  Thomas Fong, Kathryn Trinkaus, Douglas Adkins, Ravi Vij, Steven M Devine, Michael Tomasson, Lawrence T Goodnough, Sandra Lopez, Timothy Graubert, Shalini Shenoy, John F Dipersio, Hanna J Khoury
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  ABSTRACT: Hydroxychloroquine (HCQ) is an immunosuppressive lysosomotropic amine that has activity against graft-versus-host disease (GVHD). In a single-institution phase III trial, 95 recipients of allogeneic peripheral blood stem cell (PBSC) transplantation were randomized to receive, in a double-blind fashion, and in addition to prophylactic cyclosporine A (CSA), HCQ, or placebo starting 21 days pretransplant and continued until day +365. HCQ was very well tolerated and not associated with side effects. Overall, the incidence of acute GVHD (aGVHD) was 59% in both arms, and severe aGVHD occurred in 11% (HCQ) and 14% (placebo) (P = .76). Sixty percent and 78% of patients developed chronic GVHD (cGVHD) in the HCQ and the placebo arms, respectively (P = .15). With a median follow-up of 18 months, relapse-free and overall survivals (OS) were comparable in both groups. In summary, in this randomized trial, the addition of HCQ to single-agent CSA had no effects on aGVHD or cGVHD or survival.
  Biology of Blood and Marrow Transplantation 11/2007; 13(10):1201-6. · 3.87 Impact Factor
• Article: Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning.

  Aarati Rao, Naynesh Kamani, Alexandra Filipovich, Susan Molleran Lee, Stella M Davies, Jignesh Dalal, Shalini Shenoy
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  ABSTRACT: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, fatal autoimmune disorder caused by mutations in the FOXP3 gene leading to the disruption of signaling pathways involved in regulatory T-lymphocyte function. Lifelong multiagent immunosuppression is necessary to control debilitating autoimmune manifestations such as colitis and food allergies. Allogeneic hematopoietic stem cell transplantation (HSCT) can restore T-cell regulatory function but has been previously associated with poor outcome. We describe successful HSCT in 4 patients with IPEX syndrome using a novel reduced-intensity conditioning regimen that resulted in stable donor engraftment, reconstitution of FOXP3+ T regulatory CD4+ cells, and amelioration of gastrointestinal symptoms.
  Blood 02/2007; 109(1):383-5. · 9.90 Impact Factor
• Article: Granulocyte-colony-stimulating factor-mobilized prophylactic granulocyte transfusions given after allogeneic peripheral blood progenitor cell transplantation result in a modest reduction of febrile days and intravenous antibiotic usage.

  Aarti Oza, Chris Hallemeier, Lawrence Goodnough, Hanna Khoury, Shalini Shenoy, Steven Devine, Kristan Augustin, Ravi Vij, Kathryn Trinkaus, John F Dipersio, Douglas Adkins
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  ABSTRACT: It was hypothesized that transfusion of two granulocyte-colony-stimulating factor (G-CSF)-mobilized prophylactic granulocyte components into allogeneic peripheral blood progenitor cell (PBPC) transplant patients during the regimen-related neutropenic interval would result in clinical benefit. HLA-matched sibling PBPC donors (n=151) were biologically randomized based on ABO mismatch to donate granulocyte components (Cohort G) or not donate granulocytes (control group, Cohort C). ABO-matched donors who did not meet other study-specific criteria were reassigned to Cohort C. Feasibility, defined as the proportion of ABO-matched donors who underwent granulocyte collections, was 42 percent (53 of 125). The percentage of patients who developed fever during the initial hospitalization was greater in Cohort C versus Cohort G (82.7% vs. 64.2%; p=0.03). In the interval from when granulocyte transfusions were initially given in Cohort G (Day +3 or Day +5) until neutrophil engraftment, the number of febrile days was less in Cohort G versus Cohort C (median, 0 vs. 1; Mann-Whitney p=0.003). The median number of days of intravenous antibiotics given during the initial hospitalization was less in Cohort G versus Cohort C (9 vs. 11; Mann-Whitney p=0.03), a difference accounted for in the interval from Day +3 or Day +5 to neutrophil recovery. There was no significant difference in length of the initial hospital stay, acute graft-versus-host disease rates, or 100-day survival between the two cohorts. This prospective study demonstrates a modest, but significant, benefit of G-CSF-mobilized HLA-matched prophylactic granulocyte transfusions in neutropenic allogeneic PBPC recipients.
  Transfusion 02/2006; 46(1):14-23. · 3.22 Impact Factor
• Article: Donor CMV serostatus has no impact on CMV viremia or disease when prophylactic granulocyte transfusions are given following allogeneic peripheral blood stem cell transplantation.

  Ravi Vij, John F DiPersio, Partha Venkatraman, Kathryn Trinkaus, Lawrence T Goodnough, Randy A Brown, Hanna J Khoury, Steven M Devine, Aarti Oza, Shalini Shenoy, William Blum, Douglas Adkins
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  ABSTRACT: We studied the impact of donor cytomegalovirus (CMV) serologic status on CMV viremia and disease when prophylactic granulocyte colony-stimulating factor (G-CSF)-mobilized granulocyte transfusions (GTs) were given following allogeneic peripheral blood stem cell (AlloPBSC) transplantation. A cohort of 83 patients who received 2 prophylactic GTs from ABO-compatible stem cell donors following AlloPBSC transplantation was compared with a cohort of 142 patients who did not. AlloPBSC donors were eligible for granulocyte donation irrespective of their CMV serostatus. Recipients received no prophylactic therapy for CMV. Donor CMV serostatus had no impact on CMV viremia and disease in the 2 cohorts. Our data show that in an era of effective surveillance and preemptive therapy for CMV, AlloPBSC recipients can safely receive 2 transfusions of prophylactic G-CSF-mobilized granulocyte components from CMV-seropositive AlloPBSC donors. This knowledge may help expand the donor pool in areas with a high prevalence of CMV in the general population.
  Blood 04/2003; 101(5):2067-9. · 9.90 Impact Factor
• Article: SUCCESSFUL BONE MARROW TRANSPLANTATION FOR IPEX SYNDROME FOLLOWING REDUCED INTENSITY CONDITIONING

  Aarati Rao, Naynesh Kamani, Alexandra Filipovich, Susan Molleran Lee, Stella M Davies, Jignesh Dalal, Shalini Shenoy