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Ann M Leen,
Catherine M Bollard,
Adam M Mendizabal,
Elizabeth J Shpall,
Paul Szabolcs,
Joseph H Antin, Neena Kapoor,
Sung-Yun Pai,
Scott D Rowley,
Partow Kebriaei,
Bimalangshu R Dey,
Bambi J Grilley,
Adrian P Gee,
Malcolm K Brenner,
Cliona M Rooney,
Helen E Heslop
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ABSTRACT: Virus-specific T-cell lines could provide useful antiviral prophylaxis and treatment for immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus, cytomegalovirus or adenovirus. Eighteen lines were administered to 50 patients with severe, refractory illness due to infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks post-infusion were: 74.0% (95% CI: 58.5%-89.5%) for the entire group (n=50), 73.9% (51.2-96.6%) for cytomegalovirus (n=23), 77.8% for adenovirus (n=18), and 66.7% (36.9-96.5%) for Epstein-Barr virus (n=9). Only four responders had a recurrence or progression. There were no immediate infusion-related adverse events, and only two subjects developed de-novo graft-versus-host disease. Despite the disparity between the lines and their recipients, the mean frequency of virus-specific T-cells rose significantly post-infusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party virus-specific T-cells is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. (www.clinicaltrials.gov - NCT00711035).
Blood 04/2013; · 9.90 Impact Factor
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Fabio Candotti,
Kit L Shaw,
Linda Muul,
Denise Carbonaro,
Robert Sokolic,
Christopher Choi,
Shepherd H Schurman,
Elizabeth Garabedian,
Chimene Kesserwan,
G Jayashree Jagadeesh, [......],
Otto O Yang,
Arumugam Balamurugan,
Gerhard Bauer,
Joanna A Ireland,
Barbara C Engel,
Gregory M Podsakoff,
Michael S Hershfield,
R Michael Blaese,
Robertson Parkman,
Donald B Kohn
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ABSTRACT: We conducted a gene therapy trial in 10 patients with adenosine deaminase-deficient severe combined immunodeficiency (ADA-deficient SCID) using two slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pre-transplant cytoreduction and remained on ADA enzyme replacement therapy (ERT) throughout the procedure. Only transient (months), low level (<0.01%) gene marking was seen in peripheral blood mononuclear cells (PBMC) of two older subjects (15 and 20 years old), whereas some gene marking of PBMC has persisted for the past nine years in two 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 post-procedure), 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 due to poor gene marking and immune recovery and one had a subsequent allogeneic hematopoietic stem cell transplant. These studies directly demonstrate the importance of providing non-myeloablative pre-transplant conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient SCID.
Blood 09/2012; · 9.90 Impact Factor
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ABSTRACT: It is now more than 40 years since the first successful allogeneic hematopoietic stem cell transplantation (HSCT) for a child with severe combined immunodeficiency (SCID). In the succeeding years, HSCT for SCID patients have represented only a small portion of the total number of allogeneic HSCT performed. Nevertheless, the clinical and biologic importance of the patients transplanted for SCID has continued. SCID patients were the first to be successfully transplanted with nonsibling related bone marrow, unrelated bone marrow, T-cell depleted HSCT, and genetically corrected (gene transfer) autologous HSC. Many of the biologic insights now widely applied to allogeneic HSCT were first identified in the transplantation of SCID patients. This article reviews the clinical and biologic lessons that have been learned from HSCT for SCID patients, and how the information has impacted the general field of allogeneic HSCT.
Hematology/oncology clinics of North America 02/2011; 25(1):17-30. · 2.05 Impact Factor
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Claire Booth,
Kimberly C Gilmour,
Paul Veys,
Andrew R Gennery,
Mary A Slatter,
Helen Chapel,
Paul T Heath,
Colin G Steward,
Owen Smith,
Anna O'Meara, [......],
Hirokazu Kanegane,
Kim E Nichols,
I Celine Hanson, Neena Kapoor,
Elie Haddad,
Morton Cowan,
Sharon Choo,
Joanne Smart,
Peter D Arkwright,
Hubert B Gaspar
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ABSTRACT: X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.
Blood 10/2010; 117(1):53-62. · 9.90 Impact Factor
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ABSTRACT: The diagnosis of invasive aspergillus remains a challenge in the care of high-risk patients. Outcomes are improved when invasive aspergillus is diagnosed early, prompting the initiation of appropriate antifungal therapy. We evaluated the utility of prospective monitoring for invasive aspergillosis (IA) using biomarkers such as serum galactomannan (GM) and/or blood polymerase chain reaction (PCR) in high-risk pediatric patients.
Patients with high-risk leukemia (HRL) or allogenic hematopoietic cell transplant (HCT) recipients were prospectively monitored twice weekly for IA using GM and PCR for Aspergillus species.
Sixty-eight patients had collected >or=2 specimens. The 1086 specimens were collected; 627 from HRL (58%) and 459 (42%) from HCT recipients. Median specimens/patient was 11.0 (2 to 58), and median follow-up/patient was 98.5 days (14 to 437). Fifty-six percent of samples were obtained from patients receiving mold-active agents; 32% HRL and 89% HCT. There were no proven, 3 probable, and 20 possible episodes of IA. Thirteen specimens (1.2%) from 4 patients (5%) were GM+. None were positive by PCR.
The prospective use of GM and PCR in this high-risk pediatric population did not identify cases of proven IA. A high false positive rate was not detected. It is speculated that changes in clinical practice, such as early use of empiric and/or prophylactic mold-active agent and frequent imaging studies have impacted the epidemiology of IA. In a population with low incidence of IA, the use of these assays as a screening device on blood may not further enhance current outcomes.
Journal of Pediatric Hematology/Oncology 10/2009; 31(12):920-6. · 1.16 Impact Factor
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ABSTRACT: Children with severe combined immunodeficiency who receive a T cell-depleted hematopoietic stem cell transplantation (HSCT) have delayed immune reconstitution.
To examine the use of recombinant human insulin-like growth factor-I (rhIGF-I) therapy to stimulate thymopoiesis after HSCT.
A child with Omenn syndrome failed T cell reconstitution 6 months after HSCT. She started rhIGF-I therapy just before age 18 months. The initial dose (40 microg/kg twice daily) was increased every 2 weeks to a maximum dose of 120 microg/kg twice daily.
The patient's absolute T cells increased from 7 to 132/mm(3) and 662/mm(3) after 3 and 5 months of rhIGF-I therapy, respectively, and her blastogenic response to phytohemagglutinin normalized. Three months after discontinuation of rhIGF-I therapy, the T cells continued to increase (to 2,427/mm(3)) although the blastogenic response to phytohemagglutinin decreased.
This is the first known use of rhIGF-I therapy to help restore thymopoiesis in a child.
Journal of Clinical Immunology 09/2009; 30(1):114-20. · 3.08 Impact Factor
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Ami J Shah, Neena Kapoor,
Robert M Cooper,
Gay M Crooks,
Carl Lenarsky,
Hisham Abdel-Azim,
Shi Qi Wu,
Kathy Wilson,
Kenneth I Weinberg,
Robertson Parkman,
Donald B Kohn
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ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a rare autosomal recessive disorder of infancy and childhood that is invariably fatal if not treated. We report on the first patient to receive post-natal HSCT for HLH after receiving in utero chemotherapy for disease stabilization.
Pediatric Blood & Cancer 10/2008; 52(1):139-42. · 1.89 Impact Factor
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ABSTRACT: OS has been described as a clinical phenotype in infants characterized by SCID, diffuse erythroderma, and other distinct features. The pathogenesis is secondary to autologous, auto-reactive T cells produced as rare escapees from the SCID blockade. Mutations in either the RAG1 or RAG2 gene that lead to partial recombinase activity are responsible for many of the patients with these clinical features. We report on two patients, one with an atypical phenotype of OS (absence of rash but presence of other typical features) who harbored a previously undescribed mutation in RAG1, and a second who had many of the classic features of OS but was found to have a mutation in the common gamma chain (gamma(c)) cytokine receptor gene. These cases highlight the clinical and genetic heterogeneity of OS.
Pediatric Transplantation 10/2008; 13(2):244-50. · 1.48 Impact Factor
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Ami J Shah,
Karen Epport,
Colleen Azen,
Renna Killen,
Kathy Wilson,
Dominique De Clerck,
Gay Crooks, Neena Kapoor,
Donald B Kohn,
Robertson Parkman,
Kenneth I Weinberg
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ABSTRACT: 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.
Journal of Pediatric Hematology/Oncology 06/2008; 30(6):411-8. · 1.16 Impact Factor
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ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency disorder that has a variable clinical phenotype that correlates with the type of mutation in WASP, the gene encoding the WAS protein (WASP). WASP is a key regulator of actin polymerization in hematopoietic cells and has well-defined domains that are involved in signaling, cell locomotion, and immune synapse formation. Classic WAS often results from mutations that cause the absence of WASP expression, associated with thrombocytopenia with small platelets, sinopulmonary infections, and eczema in young males. Other phenotypes associated with expression of mutated WASP are X-linked thrombocytopenia and neutropenia. To date, the only curative therapy for WAS is hematopoietic cell transplantation (HCT) although gene therapy for WAS is under study. At least 2 retrospective studies of HCT for WAS have indicated that although HLA-matched sibling donors have the best outcomes (81% to 88%), when such a donor is not available, a matched unrelated donor should be considered (71% event free survival), although results are best in patients age < 5 years. Whereas most of the experience to date in Asia, Europe, and North America has been with myeloablative conditioning regimens, more recently, reduced-intensity conditioning (RIC) regimens also have been used with success. The issue of whether mixed chimerism post-HCT (which has a higher incidence in RIC transplantation) is associated with increased autoimmune manifestations in patients with WAS remains to be resolved.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2008; 15(1 Suppl):84-90. · 3.15 Impact Factor
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Neena Kapoor
Immunologic Research 02/2008; 41(1):34-44. · 3.03 Impact Factor
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ABSTRACT: To evaluate the role of BAL, CTB, and OLB in the management of pulmonary infiltrates in pediatric HSCT recipients, we conducted a retrospective review of clinical records of pediatric HSCT recipients. Data were analyzed using Chi-square for dichotomous and anova for continuous variables. Logistic regression was used to adjust confounding variables for diagnostic yield. Forty patients underwent 44 separate procedures. Infections were the prevailing cause of infiltrates with a positive diagnostic yield (96%). CTB and OLB were performed more often in patients with focal infiltrates compared with BAL (100%, 71% vs. 22%; p < 0.01). Adverse events were not significantly different across the three procedures. OLB more often yielded information that led to change in medical management (71% vs. 0%, 34%; p < 0.05) compared with CTB and BAL. Patients who had a positive diagnostic yield had no apparent survival advantage when compared with those in whom a procedure yielded no information. Logistic regression demonstrated that focal infiltrate was the only independently predictive variable for identifying a cause of pulmonary infiltrate. In conclusion, all three invasive diagnostic procedures were safe. Having a focal infiltrate was independently and significantly associated with having a positive diagnostic yield.
Pediatric Transplantation 12/2007; 11(7):736-42. · 1.48 Impact Factor
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ABSTRACT: 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.
Biology of Blood and Marrow Transplantation 05/2007; 13(5):584-93. · 3.87 Impact Factor
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Barbara C Engel,
Greg M Podsakoff,
Joanna L Ireland,
E Monika Smogorzewska,
Denise A Carbonaro,
Kathy Wilson,
Ami Shah, Neena Kapoor,
Mirna Sweeney,
Mark Borchert,
Gay M Crooks,
Kenneth I Weinberg,
Robertson Parkman,
Howard M Rosenblatt,
Shi-Qi Wu,
Michael S Hershfield,
Fabio Candotti,
Donald B Kohn
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ABSTRACT: A patient with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.
Blood 02/2007; 109(2):503-6. · 9.90 Impact Factor
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ABSTRACT: Histocompatible hematopoietic stem cell transplantation (HSCT) was conducted on a 4.5-year-old girl with Niemann-Pick disease type B. The donor was her unaffected brother. At the time of transplantation, she had severe pulmonary disease. After her first HSCT, she developed graft failure. Five years after her second HSCT, her sphingomyelinase levels are within normal levels, she has no pulmonary symptoms, and aside from persistent graft versus host disease, she is doing well.
PEDIATRICS 11/2005; 116(4):1022-5. · 4.47 Impact Factor
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Pediatric Blood & Cancer 08/2005; 45(1):82-3. · 1.89 Impact Factor
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ABSTRACT: Bone marrow transplantation (BMT) has become the standard therapy for children with relapsed acute lymphoblastic leukemia. The authors report their experience with histocompatible BMT for 52 children with acute lymphoblastic leukemia conditioned with a non-total body irradiation (TBI) regimen using busulfan and cyclophosphamide (Bu/Cy). The efficacy and long-term toxicity of the Bu/Cy regimen were determined. Overall survival was 35%. One-year, 3-year, and 7-year event-free survival rates were 54%, 33%, and 23%, respectively. Of the 52 BMT recipients, 26 relapsed. Thirteen of the relapsed patients received a second BMT and three were surviving as of this writing. The most frequent cause of death was leukemia relapse. An initial remission duration of less than 18 months was a factor in decreasing the event-free survival. The Bu/Cy regimen was well tolerated, with minimal transplant-related mortality. Neurocognitive function was tested before BMT and 1 year after BMT. When 1-year posttransplant neurocognitive test scores were compared with pretransplant scores, there was no decrease. However, there was a significant decrease in the pretransplant neurocognitive test scores in BMT recipients compared with their normal siblings. The use of Bu/Cy as a conditioning regimen for BMT does not appear to affect posttransplant neurocognitive function. Other long-term side effects, such as endocrinopathies and secondary malignancies, were also minimal. These data show that the Bu/Cy regimen is well tolerated, but the overall survival rate remains low.
Journal of Pediatric Hematology/Oncology 03/2004; 26(2):91-7. · 1.16 Impact Factor
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ABSTRACT: Bone marrow transplantation (BMT) has become the standard therapy for children with relapsed acute lymphoblastic leukemia. The authors report their experience with histocompatible BMT for 52 children with acute lymphoblastic leukemia conditioned with a non-total body irradiation (TBI) regimen using busulfan and cyclophosphamide (Bu/Cy). The efficacy and long-term toxicity of the Bu/Cy regimen were determined. Overall survival was 35%. One-year, 3-year, and 7-year event-free survival rates were 54%, 33%, and 23%, respectively. Of the 52 BMT recipients, 26 relapsed. Thirteen of the relapsed patients received a second BMT and three were surviving as of this writing. The most frequent cause of death was leukemia relapse. An initial remission duration of less than 18 months was a factor in decreasing the event-free survival. The Bu/Cy regimen was well tolerated, with minimal transplant-related mortality. Neurocognitive function was tested before BMT and 1 year after BMT. When 1-year posttransplant neurocognitive test scores were compared with pretransplant scores, there was no decrease. However, there was a significant decrease in the pretransplant neurocognitive test scores in BMT recipients compared with their normal siblings. The use of Bu/Cy as a conditioning regimen for BMT does not appear to affect posttransplant neurocognitive function. Other long-term side effects, such as endocrinopathies and secondary malignancies, were also minimal. These data show that the Bu/Cy regimen is well tolerated, but the overall survival rate remains low.
Bone marrow transplantation (BMT) has become the standard therapy for children with acute lymphoblastic leukemia (ALL) in second or greater remission. Most studies demonstrate an advantage for BMT over conventional chemotherapy for children who suffer a relapse of their leukemia, with the greatest advantage occurring for children whose relapse occurs within the first 18 months after diagnosis. 1,2
Despite intensive myeloablative therapy, the major cause of failure of BMT remains leukemia relapse. Most BMT conditioning regimens for children with ALL have used total body irradiation (TBI) and chemotherapeutic agents. Recent approaches to reducing the high rate of relapse in children with ALL following a histocompatible BMT have centered on modifications of the chemotherapeutic agents but not the elimination of TBI.
Numerous studies have shown the adverse impact of cranial irradiation on developing brains. Neurocognitive deficits seen following cranial irradiation (18-24 Gy) include declines in intelligence, academic achievement, attention, and memory. 3,4 Although decreases in neurocognitive function are well documented in patients who have received cranial irradiation, the neurocognitive function of patients who have received TBI for BMT is mixed. Some studies have shown a significant decrease in neurocognitive function after BMT, while other studies have not shown any significant impact of TBI on neurocognitive function in older children. 3-7 In addition to the effects of TBI on neurocognitive function, TBI has been known to cause many long-term effects in children, including short stature, endocrinopathies, and secondary malignancies. 8-10
The elimination of TBI from the transplant conditioning regimen might decrease some of the long-term side effects and allow more flexibility in the chemotherapeutic agents used in BMT conditioning. The combination of alkylating agents (ie, busulfan and cyclophosphamide [Bu/Cy]) was introduced into conditioning regimens for BMT approximately 20 years ago for the treatment of acute nonlymphocytic leukemia (ANLL) in adult BMT recipients. Results in children with ANLL have also shown a beneficial effect for BMT using a Bu/Cy regimen. There have been encouraging results with Bu/Cy in adults with ALL. 11,12 Davies et al 13 recently reviewed the International Bone Marrow Transplant Registry data of more than 600 children with ALL who received a histocompatible sibling BMT and reported that the 3-year leukemia-free survival rate for Bu/Cy was inferior to TBI/Cy (35% vs. 50%). However, no long-term follow-up data were included.
In this study, we report our experience with histocompatible BMT for 52 children with ALL conditioned with a Bu/Cy regimen. We sought to determine the efficacy as well as the long-term toxicity of the Bu/Cy regimen in histocompatible BMT recipients.
Journal of Pediatric Hematology/Oncology 01/2004; 26(2):91-97. · 1.16 Impact Factor
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ABSTRACT: Despite potent intensive conditioning regimens, hematopoietic stem cell transplantation (HSCT) may fail because of either relapse of the malignancy or the rejection of the graft. We report on 27 pediatric patients who received a second HSCT from an allogeneic donor for relapsed malignancy or graft failure. One-year, 5-year, and 10-year probabilities of survival for all patients were 53%, 36%, and 24%, respectively. Twenty patients received second HSCTs for relapsed malignancy, of whom 6 were alive and disease free at the time of this report. Seven patients received a second HSCT for graft failure, of whom 3 were alive and well as of this report. Twenty-five patients were tested for immune reconstitution following their second HSCT. Sixteen patients developed antigen-specific T-lymphocyte responses; the median time to development of antigen-specific responses was 13 months. There was no significant neurocognitive decline in patients tested 1 to 3 years following their second HSCT. Endocrine evaluations revealed deficiencies in growth hormone (7 patients), gonadal function (3 patients), and thyroid function (2 patients). Three patients developed significant abnormalities of tooth development, including absence of secondary teeth. These results show that a second HSCT offers curative therapy for selected pediatric patients whose first HSCT failed. Although toxicity is considerable following a second transplantation, the major causes of mortality continue to be relapse and infection.
Biology of Blood and Marrow Transplantation 02/2002; 8(4):221-8. · 3.87 Impact Factor
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ABSTRACT: The occurrence of smooth muscle neoplasms and lymphoproliferative disorders in immunocompromised patients is well recognized. We report the case of an 8-year-old girl with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) status post-bone marrow transplant (BMT), in whom Epstein-Barr virus (EBV) was detected in innumerable leiomyomas involving the gallbladder (leiomyomatosis), and multifocal leiomyomas in liver, spleen, pancreas, intestinal tract, and lung. The leiomyomas of the gallbladder, liver, spleen, and lung were asymptomatic, while those located in the colon became clinically manifest by recurrent lower intestinal hemorrhage. The patient also developed extensive EBV-associated polymorphic lymphoproliferative disorder (PTLD) in nodal and extranodal sites. In addition, there were pulmonary and gastric adenovirus and small and large intestine cryptosporidum infections. Our case appears to be the first example of leiomyomatosis of the gallbladder coexisting with multifocal leiomyomas of the liver, spleen, pancreas, intestinal tract, and lung, as well as EBV-derived lymphoproliferative disorder in a young girl with ADA-deficient SCID. Awareness of the pattern of involvement and of the coexistence of benign leiomyomatous proliferations with lymphoproliferative disorder is of value when gallbladder, pancreatic, biliary tree, lung, and intestinal lesions become clinically manifest in these patients. The demonstration of EBV infection in both leiomyomata and the PTLD suggests a common pathogenesis that may have therapeutic and prognostic implications.
Pediatric and Developmental Pathology 6(5):449-57. · 0.99 Impact Factor
