T N Small

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

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Publications (105)580.88 Total impact

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    ABSTRACT: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth.
    New England Journal of Medicine 07/2014; 371(5):434-46. · 54.42 Impact Factor
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    ABSTRACT: Cord blood transplantation (CBT) is a known risk factor for human herpesvirus-6 (HHV-6) infection. We analyzed the nature of HHV-6 infections in 125 double-unit CBT recipients (median age 42 years) transplanted for hematologic malignancies with calcineurin-inhibitor/ mycophenolate mofetil prophylaxis and no anti-thymocyte globulin (ATG). One-hundred and seventeen (94%) patients reactivated HHV-6 by quantitative plasma PCR (median peak 7,600 copies/mL, range 100-160,000) at a median of 20 days (range 10-59) after transplantation. HHV-6 encephalitis occurred in 2 patients (1.6%), of whom one died and the other recovered with therapy. There was no association between high level HHV-6 viremia (> 10,000 or > 25,000 copies/mL) and age, diagnosis, conditioning intensity, or dominant unit characteristics, or between high level viremia and transplant outcomes (engraftment, cytomegalovirus reactivation, day 100 grade II-IV acute graft-versus-host disease, day 100 transplant-related mortality, or 1-year disease-free survival). HHV-6 therapy delayed the onset of cytomegalovirus reactivation. Interestingly, HHV-6 resolution was observed in untreated patients, and resolution of viremia correlated with absolute lymphocyte count recovery. We observed a low incidence of encephalitis and no association with CBT outcomes. Our data suggests therapy in uncomplicated viremia may not be warranted. However, further investigation of the risk-benefit of HHV-6 viremia treatment and standardization of PCR testing is required.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2014; · 3.15 Impact Factor
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    ABSTRACT: The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.
    The Journal of allergy and clinical immunology 10/2013; · 12.05 Impact Factor
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    ABSTRACT: Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2013; · 2.35 Impact Factor
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    ABSTRACT: Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.
    PLoS Genetics 08/2013; 9(8):e1003695. · 8.17 Impact Factor
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    ABSTRACT: The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.
    Journal of Clinical Immunology 07/2013; · 2.65 Impact Factor
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    ABSTRACT: Adenovirus (ADV) is an important cause of viral mortality in hematopoietic stem cell transplantation (HSCT). Recipients of T cell–depleted (TCD) HSCT are at increased risk for viral infections. We compared the rates and outcomes of ADV viremia and disease between TCD and conventional (CONV) HSCT at our institution. This was an observational study of 624 adult and pediatric recipients of myeloablative HSCT at Memorial Sloan-Kettering Cancer Center between January 1, 2006, and March 11, 2011. Viral cultures and ADV PCR were ordered as clinically indicated. ADV viremia by quantitative PCR assay was defined as 1 or more positive values ≥1,000 copies/mL or 2 or more consecutive positive values. Competing-risk regression analyses were used to identify predictors for ADV viremia. ADV viremia at 1 year after HSCT occurred in 8% of TCD HSCT recipients and in 4.0% of CONV HSCT recipients (P = .041). Among the TCD recipients, ADV viremia was seen in 15% of children, compared with 5% of adults (P = .008). Young age (hazard ratio [HR], 3.0; P < .001) and acute graft-versus-host disease (GVHD) (HR, 3.2; P = .001) were identified as risk factors for ADV viremia. ADV viremia was predictive of mortality (HR, 6.0; P < .001). ADV disease developed in 3.5% of TCD HSCT recipients and in 0.4% of CONV HSCT recipients (P = .022), with an attributable mortality of 27%. Among TCD HSCY recipients, grade II to IV GVHD was a risk factor for ADV disease (HR, 13; P < .001), but age was not. More than 90% of the cases of ADV disease involved a viral load of ≥10,000 copies/mL. Rates of ADV disease were 10-fold greater in TCD HSCT recipients compared with CONV HSCT recipients, predominantly in patients who developed acute GVHD. The benefit of preemptive therapy for an ADV viral load ≥10,000 copies/mL for preventing ADV disease in TCD HSCT recipients should be evaluated in prospective clinical trials.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2013; 19(3):387–392. · 3.15 Impact Factor
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    ABSTRACT: Manifestations and risk factors of graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age 37 years) transplanted for hematologic malignancies with myeloablative or non-myeloablative conditioning and calcineurin-inhibitor/ mycophenolate mofetil immunosuppression. Incidences of day 180 grade II-IV and III-IV acute GVHD (aGVHD) were 53% (95%CI: 44-62) and 23% (95%CI: 15-31), respectively, with a median onset of 40 days (range 14-169). Eighty percent of patients with grade II-IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome, whereas late GVHD in the form of classical chronic GVHD was uncommon. Notably, grade III-IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A,-B,-DRB1 allele match was > 4/6 to the recipient (HR 0.385, p = 0.031), whereas engrafting unit infused nucleated cell dose and unit-unit HLA-match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA-match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
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    ABSTRACT: MHC Class II deficiency is a rare primary immunodeficiency disease characterized by absent HLA Class II expression resulting in CD4 lymphopenia, lack of Ag-specific responses and recurrent infection. Without successful allogeneic SCT, most children succumb to infection within the first decade of life. To date, alternative donor transplants for this disorder have been inferior to SCT for other forms of combined immunodeficiency disease due to an increased incidence of graft rejection, GVHD and death from infections generally acquired before haematopoietic cell transplantation. This study details the transplant outcome of 16 affected children consecutively transplanted at four centers since 1990, 8 of whom required mechanical ventilation pretransplant. Stem cells were derived from an HLA-mismatched family member (n=10), an HLA-matched unrelated adult donor (n=4), or an unrelated cord blood donor (n=2). Graft failure occurred in five children, all of whom underwent a second SCT. Six patients developed acute GVHD although no patient developed chronic GVHD after primary transplantation. CD4 T-cell reconstitution remained below the normal range for age, suggesting defective thymopoiesis after allo-SCT. Nonetheless, 69% of children survive without GVHD at a median follow-up of 5.7 years, indicating improved outcomes compared with previous studies.
    Bone Marrow Transplantation 09/2012; 48(2):226-232. · 3.47 Impact Factor
  • C J Forlenza, T N Small
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    ABSTRACT: Over 40 000 hematopoietic cell transplantations (HCT) are performed worldwide each year, increasing the number of transplant survivors returning to school, the work place and overseas travel. Outbreaks of measles and mumps in immunocompetent individuals and the increased morbidity associated with primary varicella and shingles in older individuals highlight the need for effective vaccination of these vulnerable patients. In current post-HCT vaccination guidelines, only the measles, mumps and rubella vaccine (MMR) and the live-attenuated varicella vaccine (LAVV) designed to prevent primary varicella in varicella zoster seronegative individuals are permissible post HCT and only in select patient groups. All other vaccines, including the shingles vaccines, are contraindicated post HCT. Current data, primarily in pediatric HCT recipients, demonstrate a 60-70% response following a single MMR or LAVV. A two-dose schedule increases the seroconversion rate following these vaccines. This review will highlight published studies on the immunogenicity of MMR and the LAVV, areas in which data on these vaccines are lacking, the criteria for their use in patients transplanted at our center and potential studies to answer questions posed by the growing number of transplant survivors and their physicians on how to safely administer live-attenuated viral vaccines.Bone Marrow Transplantation advance online publication, 13 August 2012; doi:10.1038/bmt.2012.141.
    Bone marrow transplantation 08/2012; · 3.00 Impact Factor
  • Y.J. Lee, D. Chung, K. Xiao, T. Small, E. Papadopoulos, A.A. Jakubowski, G.A. Papanicolaou
    Biology of Blood and Marrow Transplantation 02/2012; 18(2):S214-S215. · 3.35 Impact Factor
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    ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in children. The most significant clinical features of PNH include: bone marrow failure, intravascular hemolysis, and thrombosis. To further characterize the clinical presentation and outcome to treatment we performed a retrospective analysis of pediatric patients with PNH. We reviewed the medical records of 12 consecutive pediatric patients with PNH diagnosed at our institution from 1992 to 2010. Presenting clinical symptoms included: bone marrow failure (N = 10); gross hemoglobinuria with isolated red cell anemia (N = 1); and jaundice, hepatitis, and isolated thrombocytopenia (N = 1). Immunosuppressive therapy was the initial treatment for 8 patients. Five patients had myelodysplastic features without developing excessive blasts or leukemic transformation. Thrombosis occurred in 6 patients. Five patients underwent hematopoietic stem cell transplant (HSCT) of whom 3 patients are alive and disease-free. Three patients received anti-complement therapy with eculizumab. Two patients died following complications related to thrombosis and 2 patients are transfusion independent with stable disease. This report highlights a high rate of bone marrow failure along with a low rate of hemoglobinuria at presentation, a high rate of thrombosis, and for some patients the spontaneous resolution of myelodysplastic features. Delay in diagnosis is common and we recommend appropriate PNH testing in all patients with AA, MDS, unexplained Coombs-negative hemolysis, or thrombosis. While HSCT remains the only curative option the high prevalence of hemolysis and thrombosis should warrant the consideration of early treatment with anti-complement therapy.
    Pediatric Blood & Cancer 12/2011; 59(3):525-9. · 2.35 Impact Factor
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    ABSTRACT: We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell transplantation recipients with biopsy-proven EBV-lymphoproliferative disease (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions in 73% and 68% of treated patients including 74% and 72% of patients surviving ≥ 8 days after infusion, respectively. Reversible acute GVHD occurred in recipients of DLIs (17%) but not EBV-CTLs. The probability of complete response was significantly lower among patients with multiorgan involvement. In responders, DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not increase and EBV viremia persisted. Treatment failures were correlated with impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the patient's blood or biopsied tumor or they failed to lyse their targets because they were selectively restricted by HLA alleles not shared by the EBV-LPD. Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to impaired T-cell recognition of tumor-associated viral antigens or their presenting HLA alleles.
    Blood 12/2011; 119(11):2644-56. · 9.78 Impact Factor
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    ABSTRACT: Thrombosis is the major risk factor for death in patients with paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to thrombolysis. We reviewed the outcome of thrombolytic therapy for patients with paroxysmal nocturnal hemoglobinuria who had thromboses refractory to anticoagulation at our institutions. In this study of 41 patients who had at least one thrombotic event, we confirmed a very high incidence of recurrence despite anticoagulation. Nine patients with thrombosis were regarded as eligible for administration of intravenous tissue plasminogen activator, which was effective in reversing thrombi in all of 15 occasions in which it was given. Serious hemorrhagic complications developed in three cases. At last follow-up visit, of the nine patients treated, three had died, and six were in very good to excellent condition in terms of clinical outcome and radiological findings. The only patient in whom thrombolysis may have contributed to a fatal outcome also had complications of "heparin induced thrombocytopenia with thrombosis", which we diagnosed in three additional patients. In our review of the literature, nine out of 15 patients treated with thrombolysis have had a good outcome. Although it is associated with a significant but manageable risk of bleeding, systemic thrombolysis is a highly effective treatment for reversing venous thromboses in patients with paroxysmal nocturnal hemoglobinuria.
    Haematologica 12/2011; 97(3):344-52. · 5.94 Impact Factor
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    ABSTRACT: Defective immune reconstitution is a major barrier to successful hematopoietic cell transplantation (HCT), and has important implications in the pediatric population. There are many factors that affect immune recovery, including stem cell source and graft-versus-host disease (GVHD). Complete assessment of immune recovery, including T and B lymphocyte evaluation, innate immunity, and response to neoantigens, may provide insight as to infection risk and optimal time for immunizations. The increasing use of cord blood grafts requires additional study regarding early reconstitution and impact upon survival. Immunization schedules may require modification based upon stem cell source and immune reconstitution, and this is of particular importance as many children have been incompletely immunized, or not at all, before school entry. Additional studies are needed in children post-HCT to evaluate the impact of differing stem cell sources upon immune reconstitution, infectious risks, and immunization responses.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2011; 18(1):6-15. · 3.15 Impact Factor
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    ABSTRACT: The development of treatment-related myelodysplastic syndrome (tMDS) or treatment-related acute myelogenous leukemia (tAML) is a complication that can occur after chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a nonmalignant primary tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM) transplantation service for the treatment of tMDS/tAML over a 15-year period. Five patients proceeded to HSCT without induction chemotherapy. Fourteen patients received high-dose cytarabine according to the Capizzi II regimen as first-line induction therapy with 13 of them achieving complete remission (CR) or refractory anemia (RA) with persistent cytogenetic abnormalities after this treatment. Two patients received an anthracycline-based induction therapy. Conditioning regimens were selected according to previous therapies: 11 patients received busulfan-melphalan-fludarabine (BU-MEL-FLU), which consisted of busulfan (0.8 mg/kg/dose every 6 hours ×10 doses), melphalan (70 mg/m(2)/dose × two doses), and fludarabine (25 mg/m(2)/dose × five doses) for cytoreduction; three patients received a total body irradiation (TBI)-containing regimen; seven patients received myeloablative regimens containing busulfan and/or melphalan and/or thiotepa with doses modified for organ toxicity. Sixteen patients received T cell-depleted (TCD) grafts; four patients received unmodified grafts; one patient received a double-unit cord blood transplantation (DUCBT). Donors included HLA-matched (n = 9), or mismatched (n = 3) related donors, or HLA-matched (n = 4), or mismatched (n = 4) unrelated donors, or DUCBT (n = 1). Disease status at the time of HSCT was: morphologic and cytogenetic CR (n = 12); RA with positive cytogenetics (n = 6); and refractory disease (n = 3). With a median follow-up of 5.9 years (2.2-15.7 years), the 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire group were 61.1% with 12 patients alive without evidence of either primary disease or tMDS/tAML. The OS and DFS rate for the 11 patients who received the BU-MEL-FLU cytoreduction with TCD grafts was 54.5%. DFS was 65.7% for patients in RA or CR at HSCT compared with 0% for patients with >5% residual marrow blasts (P = .015). Nine patients died; the cause of death was relapse of MDS/AML (n = 4) or primary disease (n = 2), graft-versus-host disease (GVHD; n = 2), and infection (n = 1). Four patients developed grade II to IV acute GVHD. One patient developed localized chronic GVHD. Our results suggest that the strategy of induction with high-dose cytarabine therapy followed by allogeneic stem cell transplantation improves the overall outcome for patients with tMDS/tAML. In addition, the use of a TCD transplantation with BU-MEL-FLU as cytoreduction may decrease the toxicity of transplantation in heavily pretreated patients without an increase in relapse rate.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2011; 18(3):473-80. · 3.15 Impact Factor
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    ABSTRACT: Background: Adenovirus is frequently recovered from stool cultures of HSCT patients with diarrhea. ADV disease is associated with high mortality. High level or rising ADV viremia is shown to precede development of ADV disease. Since 2006 we have used quantitative ADV PCR for detection of viremia especially in patients with + stool Cx for ADV. We report the outcomes of ADV viremia in pts with pos stool cultures. Methods: Prospective observational study of 776 adult and pediatric HSCT at MSKCC from Jan 1, 2006 through Dec 2010. Minimum follow up 3 months. ADV PCR in whole blood was performed by Viracor. ADV viremia was defined as ≥1 +PCR at >1,000 copies/ml or >2 consecutive +. Early ADV: First +PCR <180 days post BMT. Results: Of 776 HSCT, 24% were children, 51.5% T-cell depleted (TCD), 80.6% myeloablative (MA), 34% marched related donor, and 29% matched unrelated donor. 9% of adults and 20.7% children had ADV in stool, while ADV viremia developed in and 3.7% and 13.1% respectively. The cumulative incidence at 1 year was 11.3% (95%CI 9-13.6) for +stool and 5.7% (95%CI 4.1-7.4) for viremia. In pts with + stool, TCD (p=0.007) and pediatric (p=0.07) were associated with viremia. We examined 37 patients [TCD 28 and conventional BMT (cBMT) 9] with viremia. Among the 28 TCD pts, 50% were adults, 71% had early ADV a median 58 days (range 15-159) post BMT. Max viral load was >1x106 copies/ml in 36%. Four (20%) pts with early ADV had grade 3-4 GVHD in contrast to 7 (88%) with late ADV. Mortality was attributable to ADV in 9 (32%) pts; 8 (89%) with max VL>106copies/ml. Among the 9 cBMT, 30% were adults, 78% had MA and 89% had early ADV a median 43 days (range 10-82) post BMT, 87.5% (7/8) had ADV< 106 copies/ml. The rate of grade 3-4 GVHD was 44.4%. There was no mortality attributable to ADV. Conclusion: 1) The cumulative incidence of stool and blood ADV at 1 year were 11.3% and 5.7% respectively.2) TCD was a risk factor for viremia in ADV stool+. 3) ADV attributable mortality was 32% in TCD and 0% in cBMT. 4) A max viral load >106 copies/ml carried a 70% attributable mortality. 5) Screening efforts for early detection of viremia should be focused in TCD HSCT particularly children.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Cord blood transplantation (CB-T) is increasingly used as a treatment alternative for hematologic malignancies. However, how CB-T compares to related (RD-T) and unrelated donor transplantation (URD-T) is not established. We compared survival of 75 double-unit CB-T, 108 RD-T, and 184 URD-T recipients who received transplants over the same period for the treatment of hematologic malignancies. Patients had similar ages and disease risk, and a similar percentage had acute leukemia. The incidence of day 180 transplant-related mortality (TRM) of 21% (95% confidence interval [CI]: 12-31) after CB-T was higher than that of RD-T recipients. However, this was compensated for by a low risk of TRM after day 180, and a relatively low incidence of relapse. Hence, the 2-year progression-free survival (PFS) of 55% (95% CI: 45-68) after CB-T was similar to that after RD-T or URD-T (P = .573). In multivariate analysis, donor source had no influence on PFS, with the only significant factors being recipient age and disease risk. In a subanalysis of 201 patients with acute leukemia, CB-T, RD-T, and URD-T recipients also had similar 2-year disease-free survival (P = .482). These data provide strong support for the further investigation of double-unit CB grafts as an alternative hematopoietic stem cell source.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2011; 17(9):1316-1326. · 3.15 Impact Factor
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    ABSTRACT: Given the high morbidity and mortality associated with meningococcal disease, in 2007 the Advisory Committee of Immunization Practices recommended immunization of all children ages 11-18 with a protein-conjugated meningococcal vaccine. There are limited data on the immunogenicity of this vaccine after allogeneic hematopoietic stem cell transplantation (allo-HCT). Since 2007, we have immunized 48 patients with the MCV4 vaccine. Two vaccinated patients who lacked follow-up titers were excluded from this analysis. Stem cells were derived from an HLA-identical sibling (n = 17) or an alternative donor (n = 29). The median time to vaccination was 2.34 years after allo-HCT. Only 7 patients responded to all 4 serogroups, and 16 patients responded to none of the serogroups. The response to serogroups A, C, Y, and W-135 was 52%, 30%, 46%, and 33%, respectively. The ability to respond to 2 or more serogroups was not affected by age, diagnosis, time to vaccination, or history of graft-versus-host disease. Receipt of a T cell-depleted graft was associated with a poorer response (P = .044). Eight of 16 patients who received a second MCV4 vaccination responded to all 4 serogroups. This retrospective study suggests that response to a single MCV4 vaccination is poor after allo-HCT. Administration of a 2-dose series, as currently recommended for patients with asplenia, complement deficiency, and HIV infection, should be evaluated in this patient population.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2011; 18(1):145-9. · 3.15 Impact Factor
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    ABSTRACT: Opportunistic pulmonary infections are a major cause of post-transplant morbidity and mortality. Among these infections, Aspergillus is a common cause of fatal pneumonia. Owing to the precarious clinical condition of many patients who acquire invasive mold infections, clinicians often treat them on the basis of radiographic findings, such as the halo sign. However, in patients who do not respond to treatment or who have uncommon presentations, bronchoscopy or lung biopsy looking for other pathogens should be considered. This study describes two cases in which the radiographic halo signs characteristic of Aspergillus were in fact due to Legionella jordanis, a pathogen that has been culture proven only in two patients previously (both of whom had underlying lung pathology) and diagnosed by serologic evidence in several other patients. In immunocompromised patients, Legionella can present as a cavitary lesion. Thus, presumptive treatment for this organism should be considered in post-transplant patients who do not have a classic presentation for invasive fungal infection and/or who fail to respond to conventional treatment. These cases illustrate the importance of obtaining tissue cultures to differentiate among the wide variety of pathogens present in this patient population.
    Bone marrow transplantation 08/2011; 46(8):1166. · 3.00 Impact Factor

Publication Stats

3k Citations
580.88 Total Impact Points

Institutions

  • 1988–2013
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medicine
      • • Department of Pediatrics
      • • Bone Marrow Transplant Service
      New York City, New York, United States
  • 2002
    • American Society of Hematology
      San Francisco, California, United States