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1.
Transplant Cell Ther ; 29(6): 380.e1-380.e9, 2023 06.
Article in English | MEDLINE | ID: mdl-36990222

ABSTRACT

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34+ cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.


Subject(s)
Central Nervous System Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Child , Retrospective Studies , Autografts/chemistry , Neoplasm Recurrence, Local/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Antigens, CD34/analysis , Central Nervous System Neoplasms/therapy , Central Nervous System Neoplasms/etiology
2.
Pediatr Blood Cancer ; 70 Suppl 2: e30080, 2023 05.
Article in English | MEDLINE | ID: mdl-36349564

ABSTRACT

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow-up of these patients. Initial workup for staging is mainly performed by cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP-RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international groups, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.


Subject(s)
Kidney Neoplasms , Wilms Tumor , Child , Humans , Kidney Neoplasms/pathology , Wilms Tumor/pathology , Tomography, X-Ray Computed , Europe , Neoplasm Staging
3.
Cancer ; 128(13): 2493-2503, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35383900

ABSTRACT

BACKGROUND: An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses. METHODS: Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system. RESULTS: Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54). CONCLUSIONS: A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia.


Subject(s)
Kidney Neoplasms , Wilms Tumor , Anaplasia/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Humans , Infant , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Neoplasm Staging , Nephrectomy , Prospective Studies , Vincristine , Wilms Tumor/drug therapy , Wilms Tumor/pathology , Wilms Tumor/surgery
4.
J Pediatr Hematol Oncol ; 43(6): e832-e840, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34397617

ABSTRACT

BACKGROUND: We sought to compare survival outcomes of sarcomas in the pediatric and adolescent/young adult populations with universal care access in the Military Health System (MHS) to those from the United States general population. METHODS: We compared data from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program on the overall survival of patients 24 years or younger with histologically or microscopically confirmed sarcoma between diagnosed between January 1, 1987, and December 31, 2013. The Kaplan-Meier survival curves were used to compare survival between the 2 patient populations. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing ACTUR relative to SEER. RESULTS: The final analysis included 309 and 1236 bone sarcoma cases and 465 and 1860 soft tissue sarcoma cases from ACTUR and SEER, respectively. Cox proportional hazards analysis showed soft tissue sarcoma patients in ACTUR had significantly better overall (HR=0.73, 95% CI=0.55-0.98) and 5-year overall (HR=0.63, 95% CI=0.46-0.86) survival compared with SEER patients, but no significant difference in overall or 5-year overall survival between ACTUR and SEER patients with bone sarcoma. CONCLUSION: Survival data from the ACTUR database demonstrated significantly improved overall survival for soft tissue sarcomas and equivalent survival in bone sarcomas compared with that reported by SEER.


Subject(s)
Bone Neoplasms/epidemiology , Sarcoma/epidemiology , Soft Tissue Neoplasms/epidemiology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Kaplan-Meier Estimate , Male , Military Health Services , SEER Program , Survival Analysis , United States/epidemiology , Young Adult
5.
J Pediatr Hematol Oncol ; 43(7): e1003-e1009, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-32925411

ABSTRACT

Skewed drug metabolism of 6-mercaptopurine (6-MP) can jeopardize antileukemic effects and result in toxicities during the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing toxicities. Over 75% of our patients with acute lymphoblastic leukemia or lymphoblastic lymphoma experienced a 6-MP-related toxicity. Review of metabolite date a showed 6-methylmercaptopurine nucleotide levels were >10,000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated in 12 of 23 shunters with resolution of toxicities. We propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with inappropriate 6-MP metabolism.


Subject(s)
Algorithms , Allopurinol/pharmacology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Lymphoma, Non-Hodgkin/drug therapy , Mercaptopurine/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Antimetabolites , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/metabolism , Child , Child, Preschool , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/metabolism , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/pathology , Male , Mercaptopurine/adverse effects , Mercaptopurine/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Retrospective Studies , Young Adult
6.
J Clin Oncol ; 38(14): 1558-1568, 2020 05 10.
Article in English | MEDLINE | ID: mdl-32134700

ABSTRACT

PURPOSE: AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes. PATIENTS AND METHODS: Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I. RESULTS: Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5. CONCLUSION: VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Irinotecan/therapeutic use , Vincristine/therapeutic use , Wilms Tumor/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Child , Child, Preschool , Female , Humans , Irinotecan/pharmacology , Male , Neoplasm Staging , Pediatrics , Vincristine/pharmacology , Young Adult
7.
Eur J Cancer ; 118: 58-66, 2019 09.
Article in English | MEDLINE | ID: mdl-31325873

ABSTRACT

BACKGROUND: In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10) or diffuse (n = 19) anaplastic Wilms' tumour (AWT) treated with vincristine and dactinomycin without flank radiation were 69.5% and 82.6%, respectively. The Children's Oncology Group AREN0321 study evaluated whether adding doxorubicin and flank radiation improves survival for these patients. PATIENTS AND METHODS: Tumour histology and stage were confirmed by real-time central pathology, surgery and radiology review. The patients received 25 weeks of vincristine, dactinomycin and doxorubicin (cumulative dose 150 mg/m2) with flank radiation (1080 cGy). We retrospectively analysed outcomes of all patients with stage I AWT enrolled in NWTSs 1-5 and AREN0321 with respect to treatment regimens. RESULTS: Eighteen patients with stage I AWT (8 focal and 10 diffuse) were enrolled on AREN0321. With a median follow-up of 4.6 years, the 4-year EFS and OS were 100%. One patient with diffuse AWT had pulmonary relapse 4.12 years after diagnosis. In the 112 patients with stage I AWT treated in NWTSs 1-5 and AREN0321, the EFS was significantly improved with doxorubicin treatment (p = 0.01; 4-year EFS: 97.2% [95% confidence interval {CI}: 91.3-100] vs. 77.5% [95% CI: 67.6-87.4]) but not by flank radiation (p = 0.15). CONCLUSIONS: Treatment of stage I AWT with vincristine, dactinomycin, doxorubicin and flank radiation in AREN0321 yielded excellent survival outcomes. Retrospective analysis of AREN0321 and NWTS patients suggests that doxorubicin had a greater contribution to the excellent outcomes than radiation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dactinomycin/administration & dosage , Doxorubicin/administration & dosage , Kidney Neoplasms/therapy , Vincristine/administration & dosage , Wilms Tumor/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Child , Child, Preschool , Dactinomycin/adverse effects , Disease Progression , Doxorubicin/adverse effects , Female , Humans , Infant , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Neoplasm Staging , Nephrectomy , Progression-Free Survival , Radiotherapy, Adjuvant , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , United States , Vincristine/adverse effects , Wilms Tumor/mortality , Wilms Tumor/secondary
8.
Bone Marrow Transplant ; 53(5): 535-555, 2018 05.
Article in English | MEDLINE | ID: mdl-29343837

ABSTRACT

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following 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 to 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. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.


Subject(s)
Cognitive Dysfunction/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Bone Marrow Transplantation/adverse effects , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/therapy , Humans , Long Term Adverse Effects , Quality of Life , Risk Factors , Transplant Recipients
9.
Cancer ; 124(4): 816-825, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29125192

ABSTRACT

BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described. METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for ≥2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years. RESULTS: The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population. CONCLUSIONS: Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications. Cancer 2018;124:816-25. © 2017 American Cancer Society.


Subject(s)
Cancer Survivors/statistics & numerical data , Hematopoietic Stem Cell Transplantation/methods , Hodgkin Disease/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Adolescent , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Time Factors , Transplantation, Autologous , Young Adult
10.
Biol Blood Marrow Transplant ; 23(8): 1342-1349, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28450183

ABSTRACT

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children < 10 years of age (n = 4412; 59%), whites (n = 5787; 77%), and children with a performance score ≥ 90% at HSCT (n = 6187; 83%). Leukemia was the most common indication for an allo-transplant (n = 4170; 94%), and among these, acute lymphoblastic leukemia in second complete remission (n = 829; 20%) and acute myeloid leukemia in first complete remission (n = 800; 19%) werethe most common. The most frequently used donor relation, stem cell sources, and HLA match were unrelated donor (n = 2933; 67%), bone marrow (n = 2378; 54%), and matched at 8/8 HLA antigens (n = 1098; 37%) respectively. Most allo-transplants used myeloablative conditioning (n = 4070; 92%) and calcineurin inhibitors and methotrexate (n = 2245; 51%) for acute graft-versus-host disease prophylaxis. Neuroblastoma was the most common primary neoplasm for an auto-transplant (n = 1338; 44%). Tandem auto-transplants for neuroblastoma declined after 2012 (40% in 2011, 25% in 2012, and 8% in 2014), whereas tandem auto-transplants increased for brain tumors (57% in 2008 and 77% in 2014). Allo-transplants from relatives other than HLA-identical siblings doubled between 2008 and 2014 (3% in 2008 and 6% in 2014). These trends will be monitored in future reports of transplant practices in the United States.


Subject(s)
Brain Neoplasms/therapy , Calcineurin Inhibitors/administration & dosage , Hematopoietic Stem Cell Transplantation , Methotrexate/administration & dosage , Neuroblastoma/therapy , Transplantation Conditioning/methods , Adolescent , Allografts , Autografts , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies
11.
Mil Med ; 181(10): 1294-1299, 2016 10.
Article in English | MEDLINE | ID: mdl-27753566

ABSTRACT

BACKGROUND: Many medical institutions have moved forward with curricular objectives aimed at teaching professionalism, but the question remains: are we teaching the most appropriate content at the most opportune times to maximize sustained learning? The students' point of view of professionalism is helpful in addressing this question. AIM: To describe the views of professionalism held by students and faculty at the Uniformed Services University of the Health Sciences. METHODS: In e-mailed surveys, students and faculty free-texted the three most important characteristics of a professional. Qualitative analysis was used to analyze the results. Data were compared on the basis of the percentage of each group affirming one of the characteristics. RESULTS: Fourteen characteristics of professionalism were found. There were significant differences across all participant groups in the characteristics that each indicated were most important. CONCLUSION: Differences emerge between definitions of professionalism that appear to relate to training and experience. Students' views of professionalism reflect the immediate context of their educational environment. Curricula targeted to the students' foci are relevant in teaching professionalism.


Subject(s)
Attitude of Health Personnel , Curriculum/trends , Education, Medical, Undergraduate/methods , Education, Medical, Undergraduate/standards , Professionalism/standards , Humans , Patient-Centered Care/methods , Qualitative Research , Students, Medical/statistics & numerical data , Surveys and Questionnaires , Universities/standards
12.
J Pediatr Hematol Oncol ; 38(2): 147-51, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26808368

ABSTRACT

6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels. We suggest that this combination therapy can be used safely to change the metabolite production in patients who develop excessive hepatotoxicity.


Subject(s)
Allopurinol/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites/administration & dosage , Mercaptopurine/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/metabolism , Child , Humans , Liver/drug effects , Maintenance Chemotherapy/methods , Male , Mercaptopurine/administration & dosage , Mercaptopurine/metabolism
13.
Biol Blood Marrow Transplant ; 21(1): 151-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25316109

ABSTRACT

We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Myeloablative Agonists/therapeutic use , Myelodysplastic Syndromes/therapy , Transplantation Conditioning , Adolescent , Adult , Aged , Cataract/etiology , Cataract/immunology , Cataract/pathology , Child , Chronic Disease , Female , Graft vs Host Disease/drug therapy , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunosuppressive Agents/therapeutic use , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Longitudinal Studies , Male , Middle Aged , Myelodysplastic Syndromes/immunology , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Osteonecrosis/etiology , Osteonecrosis/immunology , Osteonecrosis/pathology , Recurrence , Survival Analysis , Time Factors , Transplantation, Homologous , Treatment Outcome , Unrelated Donors
14.
Pediatr Infect Dis J ; 34(4): 445-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25259934

ABSTRACT

We report a case of a catheter-related bloodstream infection with Mycobacterium frederiksbergense in an immunocompromised child with acute lymphoblastic leukemia. Nontuberculous mycobacteria have been implicated in central venous catheter infections in immunosuppressed individuals, however, to our knowledge this is the first reported case of invasive infection with this organism.


Subject(s)
Bacteremia/diagnosis , Immunocompromised Host , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium/isolation & purification , Bacteremia/microbiology , Child, Preschool , Humans , Male , Mycobacterium Infections, Nontuberculous/microbiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
15.
J Pediatr Hematol Oncol ; 35(4): 267-70, 2013 May.
Article in English | MEDLINE | ID: mdl-23612377

ABSTRACT

Paraneoplastic syndromes may affect the central and peripheral nervous system of adults and children with cancer. Neurological symptoms may resolve with treatment of the underlying neoplasm. We report the case of a child with Wilms tumor who presented with generalized weakness, fatigue, ptosis, hypokinesis, dysarthria, urinary retention, facial diplegia, ophthalmoplegia, and autonomic dysfunction. Routine electrodiagnostic testing, including repetitive nerve stimulation, was normal. Clinical features and stimulation single-fiber electromyogram were consistent with a neuromuscular junction transmission disorder, likely Lambert-Eaton myasthenic syndrome. The child's neurological status returned to normal with successful treatment of the tumor.


Subject(s)
Kidney Neoplasms/diagnosis , Lambert-Eaton Myasthenic Syndrome/diagnosis , Wilms Tumor/diagnosis , Child, Preschool , Humans , Kidney Neoplasms/therapy , Lambert-Eaton Myasthenic Syndrome/therapy , Male , Wilms Tumor/therapy
16.
Pediatr Blood Cancer ; 60(2): 237-41, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22745043

ABSTRACT

BACKGROUND: Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. PROCEDURE: Pemetrexed, at a dose of 1910 mg/m(2) , was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B(12) , daily multivitamin supplementation, and dexamethasone. A two-stage design (10 + 10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. RESULTS: Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3-23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1-13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4-13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n = 1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). CONCLUSIONS: Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Glutamates/therapeutic use , Guanine/analogs & derivatives , Neoplasms/drug therapy , Adolescent , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Child , Child, Preschool , Female , Glutamates/administration & dosage , Glutamates/adverse effects , Guanine/administration & dosage , Guanine/adverse effects , Guanine/therapeutic use , Humans , Infusions, Intravenous , Male , Pemetrexed , Treatment Outcome , Young Adult
18.
Expert Rev Anticancer Ther ; 11(7): 1105-13, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21806333

ABSTRACT

Since Wilms' tumor occurs rarely in adults, there are no standard treatments available. Most adult patients will be diagnosed unexpectedly following nephrectomy for presumed renal cell carcinoma. Outcome for adults is inferior compared with children, although better results are reported when treated within pediatric trials. Multiple factors, including the unfamiliarity of adult oncologists and pathologists with Wilms' tumors, lack of standardized treatment and consequent delays in initiating the appropriate risk-adapted therapy, may contribute to the poor outcome. A standardized approach for the management of adult Wilms' tumors is proposed with the aim to limit treatment delay after surgery and encourage a uniform approach for this rare disease and thereby improve survival. These recommendations are based on discussions held with representatives of the renal tumor committees of the Society of Paediatric Oncology and Children's Oncology Group, and have been updated with a review of more recently published institutional and trial experience of adults treated on pediatric protocols. They provide a critical evaluation of the current evidence for the management of adult Wilms' tumors and propose details of how current pediatric therapeutic guidelines could be adapted for use in adults.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Kidney Neoplasms/surgery , Wilms Tumor/surgery , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/epidemiology , Kidney Neoplasms/pathology , Male , Middle Aged , Practice Guidelines as Topic , Prognosis , Treatment Outcome , Wilms Tumor/drug therapy , Wilms Tumor/epidemiology , Wilms Tumor/pathology , Young Adult
19.
J Pediatr Hematol Oncol ; 33(3): e127-31, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21399527

ABSTRACT

A 5.5-year-old asymptomatic Hispanic/African American male presented with matted lymph nodes in the neck and reticulonodular opacities in the right upper lung. An extensive diagnostic work up was performed to rule out infectious etiologies. Biopsies of the lymph node and lung tissue were diagnostic of nodular lymphocyte predominant Hodgkin lymphoma. Two weeks into the chemotherapy, gastric aspirates grew Mycobacterium avium intracellulare. This is the first case of nodular lymphocyte predominant Hodgkin lymphoma involving the lung with coexistent Mycobacterium avium intracellulare.


Subject(s)
Hodgkin Disease/complications , Lung Neoplasms/complications , Lymph Nodes/pathology , Lymphocytes/pathology , Mycobacterium avium-intracellulare Infection/complications , Child, Preschool , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/pathology , Positron-Emission Tomography
20.
Biol Blood Marrow Transplant ; 17(2): 157-66, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20659574

ABSTRACT

Preservation of fertility after hematopoietic cell transplantation (HCT) can have a significant influence on the quality of life of transplant survivors. We describe 178 pregnancies in HCT recipients that were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2002 and 2007. There were 83 pregnancies in female HCT recipients and 95 pregnancies in female partners of male HCT recipients. Indications for transplantation included hematologic and other malignancies (N = 99) and nonmalignant disorders (N = 79, of which 75 patients had severe aplastic anemia). The cohort included recipients of autologous HCT (20 women, 13 men), myeloablative (MA) allogeneic HCT (12 women, 50 men), and nonmyeloablative allogeneic HCT (2 women, 2 men). Age at HCT was <20 years for 50% of women and 19% of men. Conditioning regimens included total body irradiation (TBI) in 16% of women and 19% of men; doses were MA in 10% of women and in 16% of men. Live births were reported in 86% of pregnancies in partners of male transplant patients and 85% of pregnancies in female transplant patients, with most pregnancies occurring 5 to 10 years after HCT. We conclude that some HCT recipients can retain fertility, including patients who have received TBI and/or MA conditioning. Young patients undergoing HCT should be counseled both before and after HCT about potential loss of fertility, methods for preserving fertility, and planning for future pregnancy. Fertility and outcomes of pregnancy after HCT need prospective evaluation in large transplant cohorts.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Infertility/prevention & control , Adult , Aging , Child , Child, Preschool , Female , Humans , Infertility/etiology , Male , Middle Aged , Pregnancy , Pregnancy Outcome , Quality of Life , Sexual Partners , Transplantation Conditioning , Young Adult
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