Kyung-Nam Koh, Jung Woo Han, Hyoung Soo Choi, Hyoung Jin Kang, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Kyung Taek Hong, Jung Yoon Choi, Sung Han Kang, Hyery Kim, Ho Joon Im, Seung Min Hahn, Chuhl Joo Lyu, Hee-Jo Baek, Hoon Kook, Kyung Mi Park, Eu Jeen Yang, Young Tak Lim, Seongkoo Kim, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Meerim Park, Hyeon Jin Park, Byung-Kiu Park, Jun Ah Lee, Jun Eun Park, Soon Ki Kim, Ji Yoon Kim, Hyo Sun Kim, Youngeun Ma, Kyung Duk Park, Sang Kyu Park, Eun Sil Park, Ye Jee Shim, Eun Sun Yoo, Kyung Ha Ryu, Jae Won Yoo, Yeon Jung Lim, Hoi Soo Yoon, Mee Jeong Lee, Jae Min Lee, In-Sang Jeon, Hye Lim Jung, Hee Won Chueh, Seunghyun Won, the Korean Pediatric Hematology and Oncology Group (KPHOG)
Cancer Res Treat. 2023;55(1):279-290. Published online August 11, 2022
Purpose
Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea.
Materials and Methods
From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed.
Results
Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001).
Conclusion
The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
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Cancer Res Treat. 2022;54(1):269-276. Published online April 20, 2021
Purpose Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).
Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.
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Cancer Res Treat. 2021;53(4):1184-1194. Published online January 4, 2021
Purpose Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development.
Materials and Methods In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed.
Results Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events.
Conclusion Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.
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Cancer Res Treat. 2021;53(2):378-388. Published online October 28, 2020
Purpose Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.
Materials and Methods A search of medical records from seven centers was performed between January 2005 and December 2016.
Results Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01).
Conclusion Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.
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Cancer Res Treat. 2019;51(1):357-367. Published online May 14, 2018
Purpose
Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients.
Materials and Methods
Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected.
Results
Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis.
Conclusion
Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.
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Cancer Res Treat. 2014;46(4):358-365. Published online July 21, 2014
Purpose
Despite the rapid improvement in survival rate from Burkitt lymphoma and mature B-cell lymphoblastic leukemia (B-ALL) in children, a small subset of patients do not respond to first-line chemotherapy or experience relapse (RL). Herein, we report the clinical characteristics and outcomes of these patients.
Materials and Methods
RL or refractory Burkitt lymphoma and mature B-ALL in 125 patients diagnosed from 1990 to 2009 were retrospectively analyzed.
Results
Nineteen patients experienced RL or progressive disease (PD). Among them, 12 patients had PD or RL less than six months after initial treatment and seven had late RL. Seven patients achieved complete response (CR), 11 had PD, and one had no more therapy. Six patients who achieved CR survived without evidence of disease and four of them underwent high-dose chemotherapy (HDC) followed by stem cell transplantation (SCT). However, 11 patients who failed to obtain CR eventually died of their disease. Five-year overall survival (OS) was 31.6±10.7%. OS of patients with late RL was superior to that of patients with early RL (57.1±18.7%, vs. 16.7±10.8%, p=0.014). Achievement of CR after reinduction had significant OS (p < 0.001). OS for patients who were transplanted was superior (p < 0.01). In multivariate analysis, achievement of CR after reinduction chemotherapy showed an association with improved OS (p=0.05).
Conclusion
Late RL and chemotherapy-sensitive patients have the chance to achieve continuous CR using HDC/SCT, whereas patients who are refractory to retrieval therapy have poor prognosis. Therefore, novel salvage strategy is required for improvement of survival for this small set of patients.
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Chronic Recurrent Multifocal Osteomyelitis Associated With Inflammatory Bowel Disease Successfully Treated With Infliximab Shinhyeung Kwak, Dongsub Kim, Joon-sik Choi, Yoonsun Yoon, Eun Sil Kim, Mi Jin Kim, So-Young Yoo, Jong Sup Shim, Yon Ho Choe, Yae-Jean Kim Pediatric Infection & Vaccine.2022; 29(2): 96. CrossRef
Burkitt lymphoma Cristina López, Birgit Burkhardt, John K. C. Chan, Lorenzo Leoncini, Sam M. Mbulaiteye, Martin D. Ogwang, Jackson Orem, Rosemary Rochford, Mark Roschewski, Reiner Siebert Nature Reviews Disease Primers.2022;[Epub] CrossRef
Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis Xueqian Li, Meng Zhou, Jiaqian Qi, Yue Han Clinical Lymphoma Myeloma and Leukemia.2021; 21(3): e227. CrossRef
Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations Birgit Burkhardt, Mary Taj, Nathalie Garnier, Veronique Minard-Colin, Volkan Hazar, Karin Mellgren, Tomoo Osumi, Alina Fedorova, Natalia Myakova, Jaime Verdu-Amoros, Mara Andres, Edita Kabickova, Andishe Attarbaschi, Alan Kwok Shing Chiang, Eva Bubanska, Cancers.2021; 13(9): 2075. CrossRef
Long non-coding RNAs as the critical regulators of doxorubicin resistance in tumor cells Ghazaleh Khalili-Tanha, Meysam Moghbeli Cellular & Molecular Biology Letters.2021;[Epub] CrossRef
EBV BCL-2 homologue BHRF1 drives chemoresistance and lymphomagenesis by inhibiting multiple cellular pro-apoptotic proteins Leah Fitzsimmons, Rachel Cartlidge, Catherine Chang, Nenad Sejic, Laura C. A. Galbraith, Chathura D. Suraweera, Deborah Croom-Carter, Grant Dewson, Rosemary J. Tierney, Andrew I. Bell, Clare Shannon-Lowe, Marco J. Herold, Alan B. Rickinson, Peter M. Colma Cell Death & Differentiation.2020; 27(5): 1554. CrossRef
Treatment of relapsed/refractory paediatric aggressive B‐cell non‐Hodgkin lymphoma Maria L. Moleti, Anna M. Testi, Robin Foà British Journal of Haematology.2020; 189(5): 826. CrossRef
Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia Jin Kyung Suh, Yi-Jin Gao, Jing-Yan Tang, Shiann-Tarng Jou, Dong-Tsamn Lin, Yoshiyuki Takahashi, Seiji Kojima, Ling Jin, Yonghong Zhang, Jong Jin Seo Cancer Research and Treatment.2020; 52(2): 359. CrossRef
An 8-year retrospective study of adult and paediatric Burkitt’s lymphoma at Tygerberg Hospital, South Africa Ernest Musekwa, Zivanai C. Chapanduka, Fatima Bassa, Mariana Kruger South African Journal of Oncology.2020;[Epub] CrossRef
Rituximab is highly effective in children and adolescents with Burkitt lymphoma in Risk Groups R2 to R4 Zijun Zhen, Jia Zhu, Juan Wang, Suying Lu, Feifei Sun, Junting Huang, Xiaofei Sun Pediatric Hematology and Oncology.2020; 37(6): 489. CrossRef
Knockdown of lncRNA MCM3AP-AS1 Attenuates Chemoresistance of Burkitt Lymphoma to Doxorubicin Treatment via Targeting the miR-15a/EIF4E Axis
Chao Guo, Ming Gong, Zhenling Li Cancer Management and Research.2020; Volume 12: 5845. CrossRef
Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology Kimberly Davies, Matthew Barth, Saro Armenian, Anthony N. Audino, Phillip Barnette, Branko Cuglievan, Hilda Ding, James B. Ford, Paul J. Galardy, Rebecca Gardner, Rabi Hanna, Robert Hayashi, Alexandra E. Kovach, Andrea Judit Machnitz, Kelly W. Maloney, Li Journal of the National Comprehensive Cancer Network.2020; 18(8): 1105. CrossRef
Hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory B-cell non-Hodgkin lymphoma Naoto Fujita, Ryoji Kobayashi, Yoshiko Atsuta, Fuminori Iwasaki, Junji Suzumiya, Yoji Sasahara, Masami Inoue, Katsuyoshi Koh, Tsukasa Hori, Hiroaki Goto, Tatsuo Ichinohe, Yoshiko Hashii, Koji Kato, Ritsuro Suzuki, Tetsuo Mitsui International Journal of Hematology.2019; 109(4): 483. CrossRef
An update on Burkitt lymphoma: a review of pathogenesis and multimodality imaging assessment of disease presentation, treatment response, and recurrence Kevin Kalisz, Francesco Alessandrino, Rose Beck, Daniel Smith, Elias Kikano, Nikhil H. Ramaiya, Sree Harsha Tirumani Insights into Imaging.2019;[Epub] CrossRef
Unusual lymphoid malignancy and treatment response in two children with Down syndrome Ashley Geerlinks, Jennifer Keis, Bo Ngan, Amer Shammas, Reza Vali, Johann Hitzler Pediatric Blood & Cancer.2019;[Epub] CrossRef
Outcome of relapse in children and adolescents with B‐cell non‐Hodgkin lymphoma and mature acute leukemia: A report from the French LMB study Charlotte Rigaud, Anne Auperin, Anne Jourdain, Stephanie Haouy, Marie‐Laure Couec, Nathalie Aladjidi, Virginie Gandemer, Anne Lambliotte, Geneviève Plat, Judith Landman‐Parker, Jean Michon, Thierry Leblanc, Catherine Patte, Veronique Minard‐Colin Pediatric Blood & Cancer.2019;[Epub] CrossRef
Anti-Tumor Effect of a Novel DOX/GA-CdTe QD was Mediated by Apoptotic and Autophagic Cell Death Huaqin Zuo, Fan Wang, Di Zhou, Yi Zhou, Bing Chen, Jian Ouyang, Peipei Xu Nano.2017; 12(01): 1750011. CrossRef
Immunotherapy with the trifunctional anti-CD20 × anti-CD3 antibody FBTA05 in a patient with relapsed t(8;14)-positive post-transplant lymphoproliferative disease Anna Kieslich, Peter Ruf, Horst Lindhofer, Raynold Buhmann, Angelika Eggert, Patrick Hundsdoerfer Leukemia & Lymphoma.2017; 58(8): 1989. CrossRef
Outcomes of adults with relapsed or refractory Burkitt and high‐grade B‐cell leukemia/lymphoma Nicholas J. Short, Hagop M. Kantarjian, Heidi Ko, Joseph D. Khoury, Farhad Ravandi, Deborah A. Thomas, Guillermo Garcia‐Manero, Maria Khouri, Jorge E. Cortes, William G. Wierda, Srdan Verstovsek, Zeev Estrov, Alessandra Ferrajoli, Philip A. Thompson, Sher American Journal of Hematology.2017;[Epub] CrossRef
PURPOSE Myelodysplastic syndrome (MDS) in children needs to be elucidated in terms of clinical characteristics, natural history, the most effective treatment and prognostic factors, as the disease is very rare and its definition and classification has not reached a consensus by many physician.
This study was aimed to describe the characteristics and the disease courses of Korean children with MDS, and to analyze the usefulness of prognostic scoring systems in the prediction of transformation to acute myelogenous leukemia (AML) and overall survival among subgroups. MATERIALS AND METHODS Fourteen children with MDS seen at Chonnam University Hospital and additional 59 patients identified by the review of Korean literature were evaluated to define clinical characteristics and disease courses. Kaplan-Meier (K-M) probability of leukemic transformation and overall survival were plotted. FAB subtypes, subgroups by Boumemouth Scoring System (BSS), and International Prognostic Scoring System (IPSS) risk groups were compared to predict transformation to AML and overall survival. RESULTS The median age of 14 patients was 36.5 months. The sex ratio was 3.7:1 (M: F). The frequency of FAB subtypes in Korea was similar to that of other countries except for higher proportion of RA (37%). K-M 3-yr probability of AML transformation and survival for Korean patients were 54.7%, and 49.8%, respectively. Although FAB system, BMS and IPSS were all capable of discriminating subgroups in the prediction of AML transformation and survival, they did not reach the significant level possibly due to small number of patients assigned to each subgroup. CONCLUSION The clinical characteristics of Korean children with MDS were not different from those of other countries. This study showed the high rate of AML transformation and poor survival in children with MDS.
Patients with intermediate or high-grade non-Hodgkin's lymphoma(NHL) have been reported a 40% to 70% cure rate when treated with conventional chemotherapy or radiotherapy. However, most of the patients who do not attain complete remission(CR) or who relapae after chemotherapy are incurable using conventional salvage therapies and these individuals have potential for cure with high-dose therapy with reinfusion of stem cells derived from bone marrow or peripheral blood. Between February 1993 and September 1995, 26 patients with aggressive, relapsed and/or refractory malignant lymphoma were treated with high-dose chemotherapy with either autologous peripheral blood stem cell(25 patients) or bone marrow(l patient) support in 7 university hospitals in Korea. The median age was 39 years(range, l7 to 69) and male to female ratio was 4.2: 1. The common histologic types were diffuse large cell(42%), immunoblastic type(15%) of non-Hodgkin's lymphoma. The rate of complete remission was 61%(14/23) and overall remission rate was 78%(18/ 23) for the patients with measurable disease. Three patients were treated as the consolidation therapy in the status of complete remission. The median duration of remission was not reached right now. The median survival time was 7.8 months for all patients(the median follow up time; 9 months). The median time to recovery to a neutrophil count more than 0.5 x 10(9)/L was 13 days(range, 8 to 43), and to 1 x 10(9)/L was 22 days(range, 8 to 53). The median time to recovery of platelet count more than 50 x l0(9)/L and 100 x 10(9)/L were 20 days(range, 8 to 45) and 21 days(ranae, ll to 60). Non-hematologic side effects were fever, nausea and vomiting, and liver toxicity. Two toxic deaths occurred due to cardiovascular disease, mainly congestive heart failure. Based on high complete remission rate and tolerable toxicity, high-dose chemotherapy with hematopietic stem cell support appears to be a promising treatment modality for the patients with aggressive, relapsed and/or refractory malignant lymphoma.
Embryonal rhabdomyosarcoma arises from the embryonal mesenchyme that differentiates into striated skeletal muscle, and about 15 to 20% of rhabdomyosarcomas are genitourinary in origin. Rhabdomyosarcoma of urogenital origin occurs at 2 age peaks: one in children between 2 and 6 year old and the other during adolescence between ages 15 and 19 year old. We report a case of embryonal rhabdomyosarcoma of the bladder in a 3-year-old male. He presented dysuria with straining and dribbling, and diagnosis was made by cystoscopy and biopsy. Since partial cystectomy was performed, and he has being received continuous Pulse VAC chemotherapy with radiotherapy.
The CD34 antigen is a 115 kDa glycoprotein that marks 1%-4% of human bone marrow cells, including virtually all committed progenitor cells and long-term reconstituting stem cells. The selection of CD34+ cells may be useful in several areas of clinical stem cell transplantation, including purging of tumor cells, T cell depletion, stem cell expansion and gene therapy. Using immunomagnetic beads method (Isolex-50TM), we report hereby the first two Korean experiences of CD34+ selected peripheral blood stem cell (PBSC) transplantations. As a mean of tumor cell purging, CD34+ cells were positively selected from mobilized PBPCs and infused to a 5-year-old girl with a relapsed stage IV neuroblastoma with resultant early short-term trilineage hematopoietic recovery. In the second patient with chronic myelogenous leukemia who showed poor graft function after having underwent an initial partially-matched bone marrow transplant, CD34+ selected allogeneic PBSC transplantation was attempted to reduce the likelihood of inducing graft-versus-host disease. Augmentation of marrow function was noted with infused PBSCs which were depleted of T cells to the degree of log3.65. As CD34+ selected PBSCs are capable of restoring hematopoietic recovery after high dose therapy, further development of selection technique to ensure high purging efficiency without significant loss of stem cells and further identification of best mobilizing and conditioning regimens are required in this new field of clinical transplantation.
We experienced two cases of engraftment syndrome (ES) in a 17-year-old boy with malignant lymphoma and in a 53-year-old female patient with small cell lung cancer following peripheral blood stem cell auto-transplantation. ES is a reproducible clinical constellation of fever, skin rash, capillary leak and pulmonary infiltrates without infection, characteristically observed during engraftment in patients undergoing autoglogous bone marrow or peripheral stem cell transplantation. The incidence of ES has been reported to be about 60%. The early recognition of ES followed by administration of steroids might obviate the unnecessary use of antibiotics and help improve clinical manifestaions in the critical post-transplant neutropenic period.