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Ami Shah, MD

  • Ami Jayant Shah



Work and Education

Professional Education

University of North Carolina Chapel Hill, Chapel Hill, NC, 5/13/1990


Childrens Hospital Los Angeles Pediatric Residency, Los Angeles, CA, 6/30/1991


Childrens Hospital Los Angeles Pediatric Residency, Los Angeles, CA, 6/30/1993


Childrens Hospital Los Angeles Pediatric Residency, Los Angeles, CA, 6/30/1996

Board Certifications

Pediatric Hematology-Oncology, American Board of Pediatrics

Conditions Treated

Late effects and survivorship

Metabolic Disorders

Pediatric Leukemia

Stem Cell Transplant

All Publications

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. The New England journal of medicine Eichler, F., Duncan, C., Musolino, P. L., Orchard, P. J., De Oliveira, S., Thrasher, A. J., Armant, M., Dansereau, C., Lund, T. C., Miller, W. P., Raymond, G. V., Sankar, R., Shah, A. J., Sevin, C., Gaspar, H. B., Gissen, P., Amartino, H., Bratkovic, D., Smith, N. J., Paker, A. M., Shamir, E., O'Meara, T., Davidson, D., Aubourg, P., Williams, D. A. 2017; 377 (17): 163038


Background In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. Methods We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. Results A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. Conclusions Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM number, NCT01896102 ; number, 2011-001953-10 .).

View details for DOI 10.1056/NEJMoa1700554

View details for PubMedID 28976817

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Group for Blood and Marrow Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Kelly, D. L., Buchbinder, D., Duarte, R. F., Auletta, J. J., Bhatt, N., Byrne, M., Gabriel, M., Mahindra, A., Norkin, M., Schoemans, H., Shah, A. J., Ahmed, I., Atsuta, Y., Basak, G. W., Beattie, S., Bhella, S., Bredeson, C., Bunin, N., Dalal, J., Daly, A., Gajewski, J., Gale, R. P., Galvin, J., Hamadani, M., Hayashi, R. J., Adekola, K., Law, J., Lee, C. J., Liesveld, J., Malone, A. K., Nagler, A., Naik, S., Nishihori, T., Parsons, S. K., Scherwath, A., Schofield, H. L., Soiffer, R., Szer, J., Twist, I., Warwick, A., Wirk, B. M., Yi, J., Battiwalla, M., Flowers, M. E., Savani, B., Shaw, B. E. 2017


Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

View details for DOI 10.1016/j.bbmt.2017.09.004

View details for PubMedID 28939455

Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report. Biology of blood and marrow transplantation Chow, E. J., Anderson, L., Baker, K. S., Bhatia, S., Guilcher, G. M., Huang, J. T., Pelletier, W., Perkins, J. L., Rivard, L. S., Schechter, T., Shah, A. J., Wilson, K. D., Wong, K., Grewal, S. S., Armenian, S. H., Meacham, L. R., Mulrooney, D. A., Castellino, S. M. 2016; 22 (5): 782-795


Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines ( for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialists, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD.

View details for DOI 10.1016/j.bbmt.2016.01.023

View details for PubMedID 26802323

Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Morris, J., Rudebeck, M., Neudorf, S., Moore, T., Duerst, R., Shah, A. J., Graham, M., Aquino, V., Morris, C., Olsson, B. 2016


Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16years) and 3 dose levels (40, 60, and 80g/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-g/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen.

View details for DOI 10.1016/j.bbmt.2016.02.016

View details for PubMedID 26968792

Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Ayas, M., Eapen, M., Le-Rademacher, J., Carreras, J., Abdel-Azim, H., Alter, B. P., Anderlini, P., Battiwalla, M., Bierings, M., Buchbinder, D. K., Bonfim, C., Camitta, B. M., Fasth, A. L., Gale, R. P., Lee, M. A., Lund, T. C., Myers, K. C., Olsson, R. F., Page, K. M., Prestidge, T. D., Radhi, M., Shah, A. J., Schultz, K. R., Wirk, B., Wagner, J. E., Deeg, H. J. 2015; 21 (10): 1790-1795


A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT.

View details for DOI 10.1016/j.bbmt.2015.06.012

View details for Web of Science ID 000361781100015

View details for PubMedID 26116087

A Reduced-Toxicity Regimen Is Associated with Durable Engraftment and Clinical Cure of Nonmalignant Genetic Diseases among Children Undergoing Blood and Marrow Transplantation with an HLA-Matched Related Donor. Biology of blood and marrow transplantation Mahadeo, K. M., Weinberg, K. I., Abdel-Azim, H., Miklos, D. B., Killen, R., Kohn, D., Crooks, G. M., Shah, A. J., Kharbanda, S., Agarwal, R., Kapoor, N. 2015; 21 (3): 440-444


Blood and marrow transplantation (BMT) is a standard curative therapy for patients with nonmalignant genetic diseases. Myeloablative conditioning has been associated with significant regimen-related toxicity (RRT), whereas reduced-intensity conditioning regimens have been associated with graft failure. In this prospective pilot trial conducted at 2 centers between 2006 and 2013, we report the outcome of 22 patients with nonmalignant genetic diseases who were conditioned with a novel reduced-toxicity regimen: i.v. busulfan (16 mg/kg), alemtuzumab (52 mg/m(2)), fludarabine (140 mg/m(2)), and cyclophosphamide (105 mg/kg). The median age of the study population was 3.5 years (range, 5 months to 26 years). No cases of sinusoidal obstruction syndrome, severe or chronic graft-versus-host disease (GVHD), or primary graft failure were reported. Median time to neutrophil engraftment (>500 cells/L) and platelet engraftment (>20K cells/L) were 19 (range, 12 to 50) and 23.5 (range, 14 to 134) days, respectively. The median length of follow-up was 3 years (range, .2 to 6.3). The overall survival rates were 95% at 100 days (95% confidence interval, .72 to .99) and 90% at 6 years (95% confidence interval, .68 to .98). RRT and chronic GVHD are significant barriers to BMT for patients with nonmalignant genetic diseases. This alemtuzumab-based reduced-toxicity regimen appears to be promising with durable engraftment, effective cure of clinical disease, low rates of RRT, and no observed chronic GVHD.

View details for DOI 10.1016/j.bbmt.2014.11.005

View details for PubMedID 25459642

Unrelated donor Hematopoietic Stem Cell Transplantation for the treatment of non-malignant genetic diseases: An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection. American journal of hematology Abdel-Azim, H., Mahadeo, K. M., Zhao, Q., Khazal, S., Kohn, D. B., Crooks, G. M., Shah, A. J., Kapoor, N. 2015


Purpose Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUD), offers potentially curative therapy for patients with non-malignant genetic diseases. In this pilot study conducted from 2006-2014, we report the outcomes of 15 patients with non-malignant genetic diseases who received a myeloablative regimen with a reduced cyclophosphamide dose, adjunctive serotherapy and MUD HSCT [intravenous alemtuzumab (52mg/m(2) ), busulfan (16mg/kg), fludarabine (140mg/m(2) ) and cyclophosphamide (105mg/kg)]. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus/cyclosporine and methylprednisolone. Findings Median (range) time to neutrophil engraftment (>500 cells/L) and platelet engraftment (>20,000/mm(3) ) were 15 (12 - 28) and 25 (17 - 30) days respectively. At a median follow-up of 2 (0.2-5.4) years, the overall survival (OS) was 93.3% (95% CI: 0.61 - 0.99) and disease-free survival (DFS) was 73.3% (95% CI: 0.44 - 0.89). Among this small sample, earlier alemtuzumab clearance was significantly associated with graft rejection (p = 0.047), earlier PHA response (p =0.009) and a trend toward earlier recovery of recent thymic emigrants (RTE) (p = 0.06). Conclusion This regimen was associated with durable donor engraftment and relatively low rates of regimen related toxicity (RRT); future alemtuzumab pharmacokinetic studies may improve outcomes, by allowing targeted alemtuzumab clearance to reduce graft rejection and promote more rapid immune reconstitution. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ajh.24141

View details for PubMedID 26242764

Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report. Supportive care in cancer Effinger, K. E., Migliorati, C. A., Hudson, M. M., McMullen, K. P., Kaste, S. C., Ruble, K., Guilcher, G. M., Shah, A. J., Castellino, S. M. 2014; 22 (7): 2009-2019


Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group.An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system.The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment.Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.

View details for DOI 10.1007/s00520-014-2260-x

View details for PubMedID 24781353

Avascular Necrosis of Bone after Allogeneic Hematopoietic Cell Transplantation in Children and Adolescents BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Li, X., Brazauskas, R., Wang, Z., Al-Seraihy, A., Baker, K. S., Cahn, J., Frangoul, H. A., Gajewski, J. L., Hale, G. A., Hsu, J. W., Kamble, R. T., Lazarus, H. M., Marks, D. I., Maziarz, R. T., Savani, B. N., Shah, A. J., Shah, N., Sorror, M. L., Wood, W. A., Majhail, N. S. 2014; 20 (4): 587-592


We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were 21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication.

View details for DOI 10.1016/j.bbmt.2013.12.567

View details for Web of Science ID 000333322400023

View details for PubMedID 24388803

Cytokine and chemokine patterns across 100days after hematopoietic stem cell transplantation in children. Biology of blood and marrow transplantation DiCarlo, J., Agarwal-Hashmi, R., Shah, A., Kim, P., Craveiro, L., Killen, R., Rosenberg-Hasson, Y., Maecker, H. 2014; 20 (3): 361-369


We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT) by assaying 51 cytokines and chemokines each week for 100days in 51 children receiving allogeneic (n=44) or autologous HSCT (n=7). Assay values were reported as mean fluorescence intensity (MFI). Log transformation converted MFI to clinically relevant measures (ie, pg/mL). We searched for potential markers of transplant complications by using mixed treatment by subject analysis of variance. Global cytokine secretion in HSCT recipients was significantly lower than in concurrent control patients (n=11). Coincident with the nadir in WBC count, the concentration of many cytokines declined further by the second and third week. All analytes (except monokine induced by gamma interferon [MIG]) subsequently rebounded by week 4 (coincident with engraftment and recovery of WBC count) but often still remained well below control levels. Concurrent with the collective nadir of multiple cytokines, monocyte chemoattractant protein 1 (MCP-1), growth-regulated oncogene alpha (GRO-a), and leptin surged during weeks 2 to 4. High levels of leptin persisted throughout the 100 post-transplant days. Also during weeks 2 to 4, hepatocyte growth factor (HGF) and IL-6 surged in children with complications but not in those without complications. The peak in HGF was more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at least 2weeks before the clinical diagnosis of VOD or graft-versus-host disease (GVHD). From week 4 onward in all groups, the MFI of the cytokine resistin increased to 5 to 15 times above concurrent control. HGF has now emerged in 3 or more biomarker discovery efforts for GVHD (and in our population for VOD as well). HGF (with or without IL-6) should be investigated as a potential predictive biomarker of VOD or GVHD. Alternatively, the hyperinflammatory "signature" provided by a multicytokine assay may be predictive.

View details for DOI 10.1016/j.bbmt.2013.11.026

View details for PubMedID 24316459

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans BLOOD Candotti, F., Shaw, K. L., Muul, L., Carbonaro, D., Sokolic, R., Choi, C., Schurman, S. H., Garabedian, E., Kesserwan, C., Jagadeesh, G. J., Fu, P., Gschweng, E., Cooper, A., Tisdale, J. F., Weinberg, K. I., Crooks, G. M., Kapoor, N., Shah, A., Abdel-Azim, H., Yu, X., Smogorzewska, M., Wayne, A. S., Rosenblatt, H. M., Davis, C. M., Hanson, C., Rishi, R. G., Wang, X., Gjertson, D., Yang, O. O., Balamurugan, A., Bauer, G., Ireland, J. A., Engel, B. C., Podsakoff, G. M., Hershfield, M. S., Blaese, R. M., Parkman, R., Kohn, D. B. 2012; 120 (18): 3635-3646


We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

View details for DOI 10.1182/blood-2012-02-400937

View details for Web of Science ID 000311624800007

View details for PubMedID 22968453

Neurocognitive Function of Patients with Severe Combined Immunodeficiency IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA Shah, A. J., Kohn, D. B. 2010; 30 (1): 143-?


Hematopoietic stem cell transplantation (HSCT) has offered a curative approach for treating patients with severe combined immunodeficiency (SCID). However, HSCT may have long-term effects on some of these patients. This article reviews the literature regarding long-term neurocognitive function of patients who have received HSCT for SCID, including the effect of disease-specific characteristics, psychosocial factors, being a chronically ill child, and transplant-related factors.

View details for DOI 10.1016/j.iac.2009.10.003

View details for Web of Science ID 000279717200011

View details for PubMedID 20113891

Long-Term Neurocognitive Function of Pediatric Patients with Severe Combined Immune Deficiency (SCID): Pre- and Post-Hematopoietic Stem Cell Transplant (HSCT) JOURNAL OF CLINICAL IMMUNOLOGY Lin, M., Epport, K., Azen, C., Parkman, R., Kohn, D. B., Shah, A. J. 2009; 29 (2): 231-237


Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with severe combined immunodeficiency (SCID). The purpose of this study was to evaluate long-term neurodevelopment of patients with SCID following myeloablative chemotherapy and HSCT.Sixteen pediatric patients diagnosed with SCID were tested using the Bayley Scales of Infant Development and the validated Vineland Adaptive Behavior Scales (VABS) pre- and 1-year post-HSCT. Three years post-HSCT, there were 11 patients available for testing and four patients available 5 years post-HSCT. Patients greater than 3 years of age were administered the Wechsler Preschool and Primary Scale of Intelligence. Both raw scores and scaled scores were analyzed.There was a significant decrease 1 year post-HSCT in the Bayley Mental Developmental Index (MDI) [92.5 (pre) vs. 70.81 (1 year post), p < 0.0001] and the VABS [99.73 (pre) vs. 79.87 (1 year post), p = <0.0001]. There was a significant decrease over time in the MDI [95.00 (pre) vs. 72.64 (1 year post) vs. 71.82 (3 years post), p < 0.0001], but no significant change between 1 and 3 years post-HSCT. There was no change in the Bayley Psychomotor Development Scale (PDI) [82.4 (pre) vs. 84.8 (1 year post), p = 0.68]. The PDI scores decreased over time [86.29 (pre) vs. 86 (1 year post) vs. 74.14 (3 years post), p = 0.045]. Although there was a decrease in scaled scores, there was not a loss of skills. Analysis of raw scores showed that there was an increase in the raw test scores, which indicated that these children acquired developmental skills, but at a slower rate than normal infants and toddlers. Younger children had a more significant decrease in adaptive scores compared with older children.These findings may reflect the effects of the isolation and prolonged hospitalization that characterizes the immediate post-transplant period. Patients miss out on social interactions and learning opportunities that normally occur at their respective stages of development. These restrictions keep patients from acquiring developmentally appropriate cognitive skills as well as gross and fine motor developmental milestones. Longitudinal follow-up will be important to quantify acquisition of skills.

View details for DOI 10.1007/s10875-008-9250-z

View details for Web of Science ID 000263894600011

View details for PubMedID 18807155

Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Shah, A. J., Epport, K., Azen, C., Killen, R., Wilson, K., De Clerck, D., Crooks, G., Kapoor, N., Kohn, D. B., Parkman, R., Weinberg, K. I. 2008; 30 (6): 411-418


Neurocognitive function of pediatric patients is of great concern after hematopoietic stem cell transplantation (HSCT). We evaluated the neurocognitive function of pediatric patients pre-HSCT, 1, 3, and 5 years post-HSCT. All patients had a hematologic malignancy and received therapy to their central nervous system. Healthy siblings were tested as a comparison group. Pediatric patients with a hematologic malignancy did not have a significant decrease in their cognitive function before HSCT compared with their siblings except in areas of academic achievement. Our study population had significant declines in visual motor skills and memory test scores within the first year post-HSCT. By 3 years post-HSCT, there was an improvement in the visual motor development scores and memory scores, but there were new deficits in verbal skills. By 5 years post-HSCT, there were progressive declines in verbal skills (P=0.005), performance skills (0.04), and new deficits seen in long-term verbal memory scores (0.04). On the basis of the raw scores, most of these tests showed that patients had an inability to acquire new skills at a rate comparable to their age-matched healthy peers. However, long-term memory scores showed definite declines. The greatest decline in neurocognitive function occurred in those patients who received cranial irradiation either as part of their initial therapy or as part of their HSCT conditioning. Pediatric patients who received HSCT for hematologic malignancies have neurocognitive deficiencies that are both acute and chronic. Although some patients have acute deficits that appear and improve over time, other patients have progressive declines in neurocognitive function that are chronic.

View details for Web of Science ID 000256535200001

View details for PubMedID 18525456

The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Shah, A. J., Kapoor, N., Crooks, G. M., Weinberg, K. I., Azim, H. A., Killen, R., Kuo, L., Rushing, T., Kohn, D. B., Parkman, R. 2007; 13 (5): 584-593


Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients were evaluated for this study. Fourteen patients received Campath 1H and 13 patients received ATG. Demographics of patients who received Campath 1H consisted of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen patients received unrelated bone marrow and 1 patient received unrelated PBSC. Demographics of patients receiving ATG consisted of 9 males, 4 females with a median age of 7.4 years (21 months-19 years). Twelve patients received unrelated bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2) pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and supportive care measures were similar in both groups, including aggressive antimicrobial therapy. There was a significant difference in the incidence of severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14] versus ATG [6 of 13], P = .006). Among the patients who were transplanted for leukemia, there was no significant difference between the 2 groups in terms of relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival between the 2 groups was not significantly different. Patients receiving Campath 1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG], P = .001). The median time to the development of a normal PHA response occurred later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P = .0001). The median time to an antigen specific response also occurred later in those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P = .004). There was no significant difference between the 2 groups in terms of fungal or viral infections. Campath 1H is effective in decreasing the incidence of GVHD without increasing the risk of relapse. Although there is a significant delay in immune reconstitution, there was no increase in infectious complications or relapse in recipients of Campath 1H. Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts.

View details for DOI 10.1016/j.bbmt.2007.01.076

View details for Web of Science ID 000246252600010

View details for PubMedID 17448918