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Autologous Peripheral Blood Stem Cell Transplantation in Children and Adolescents with Non‑Hodgkin Lymphoma

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Autologous Peripheral Blood Stem Cell Transplantation in Children and Adolescents with Non‑Hodgkin Lymphoma 1826 ONCOLOGY LETTERS 10: 1826-1830, 2015 Autologous peripheral blood stem cell transplantation in children and adolescents with non‑Hodgkin lymphoma WEI GUI, LIPING SU, JIANXIA HE, LIEYANG WANG and TAO GUAN Department of Hematology, Shanxi Tumor Hospital, Taiyuan, Shanxi 030013, P.R. China Received June 14, 2014; Accepted April 14, 2015 DOI: 10.3892/ol.2015.3455 Abstract. The aim of this study was to evaluate the effect and (BL), anaplastic large-cell lymphoma and diffuse large safety of autologous peripheral blood stem cell transplantation B-cell lymphoma (2). Recent developments in chemotherapy (APBSCT) in children and adolescents with non-Hodgkin regimens, including BFM90, VDCLP and HyperCVAD/ lymphoma (NHL). Ten patients with NHL were analyzed MA, intrathecal methotraxate, cytarabine, dexamethasone retrospectively. In all the patients, lymph node enlargement and combined chemotherapy with rituximab for B-cell NHL was most frequently detected. Patients with a mediastinal mass patients, have rapidly improved the survival rate of pediatric presented with a cough, palpitation and shortness of breath. NHL patients (3-6). Long term event-free survival (EFS) has Extranodal patients presented with abdominal pain, inability been exhibited to be 60-90%. However, for ~10-30% of children to walk and vaginal bleeding. All patients underwent APBSCT with NHL who receive modern chemotherapy, the treatment is with conditioning regimens BEAM or BuCy. Among them, likely to be unsuccessful (7-10). Recently, autologous peripheral four patients with B-cell NHL received rituximab in addition blood stem cell transplantation (APBSCT), with conditioning to the conditioning regimen. Hematopoietic reconstitution was regimens BEAM or BuCy, has improved the long-term survival observed in all patients. Severe toxicity and transplant-related of children with NHL (4,9). A previous study revealed that the mortality were not observed. Prior to APBSCT, nine patients 3-year EFS in pediatric NHL patients receiving APBSCT was with a status of complete response (CR) and CR unconfirmed 70% (7). In another study, pediatric patients with refractory or achieved continuing complete remission. Only one patient relapsed NHL underwent APBSCT with conditioning regimens with partial response succumbed to progressive disease. of busulfan and cyclophosphamide and exhibited a disease-free APBSCT in children and adolescents with NHL is a safe, survival rate of 90% (11). In the present study, we explored the convenient and efficient treatment. The BEAM conditioning use of APBSCT in children and adolescents with NHL. In regimen was shown to be effective and tolerable for children total, 9 patients with a complete response (CR) status prior to and adolescents with NHL. Rituximab is a safe agent in the APBSCT survived without disease. Transplantation-associated transplantation. The CR status at the time of transplantation mortality was not observed. Furthermore, the present study demonstrated a higher survival rate. discussed 4 representative NHL cases in more detail. Introduction Patients and methods Non-Hodgkin lymphoma (NHL) is the third most common Patients. The study was approved by the ethics committee of cancer (10%), accounting for ~60% of all lymphomas in children Shanxi Tumor Hospital (Taiyuan, China). Between January 2008 and adolescents (1). The most common symptoms of pediatric and December 2013, 10 children and adolescents with NHL NHL are fever, superficial lymph node enlargement, cough, underwent APBSCT at the Department of Hematology, Shanxi shortness of breath, anorexia, abdominal pain, sore throat and Tumor Hospital. NHL was diagnosed according to the 2008 nasal obstruction. The major histological subtypes of NHL World Health Organization criteria (12) and all biopsy speci- include lymphoblastic lymphoma (LBL),oBurkitt lymphoma mens were re-evaluated in our institution. The patients were followed-up from diagnosis until mortality or the last follow-up on March 31st, 2015. The patients comprised eight males and two females. The median age was 16 years (range, 10-20 years). Most of the patients had aggressive lymphoma and were in Correspondence to: Professor Liping Su, Department of stage III/IV. Six patients were in first complete remission (CR ), Hematology, Shanxi Tumor Hospital, 3 Zhigongxinjie Street, 1 Taiyuan, Shanxi 030013, P.R. China two were in CR2, one had unconfirmed complete remission E-mail: [email protected] (CRu) and one had a partial response (PR) prior to APBSCT (Table I). Written informed consent was obtained from the Key words: peripheral blood stem cell transplantation, autologous, patients' families prior to participation in the study. non-Hodgkin lymphoma, children and adolescents, prognosis Treatment. Peripheral blood progenitor cells were mobilized by chemotherapy and granulocyte colony stimulating factor GUI Table I. Characteristics of patients with non-Hodgkin lymphoma at transplantation. et al Patient Age/ BM (blast Pathological Status before Conditioning OS : APBSCT IN CHILDREN AND ADOLESCENTS WITH NON-HODGKIN LYMPHOMA no. gender Sites of disease Stage aaIPI cells, %) type APBSCT regimen Outcome (months) 1 11/F Thoracic vertebral IVA 2 - B-LBL CR1 R-BEAM Alive with NED 45 2 11/M Ileocecum IIIA 2 - MALToma CR2 BEAM Alive with NED 78 3 10/M Inguinal lymph node IVA 2 84.5 B-LBL CR1 R-BuCy Alive with NED 46 4 15/M Cervical lymph mode, mediastinum, IVA 2 4.5 T-LBL CR1 BEAM Alive with NED 26 pleural and pericardial effusion and splenomegaly 5 20/M Cervical lymph nodes IIA 0 - B-LBL CR1 R-BEAM Alive with NED 44 6 19/M Stomach, abdominal lymph nodes IIIA 2 - GZL CR1 BEAM Alive with NED 29 and splenomegaly 7 20/M Mediastinum, pleural and pericardial IVB 3 - DLBCL CRu BEAM Alive with NED 17 effusion, ascites, cervical and abdominal lymph nodes 8 14/M Mediastinum, pleural effusion and IVB 3 4.0 T-LBL PR BEAM Dead with PD 6 cervical lymph nodes 9 17/M Pharynx, tonsil, cervical lymph IIIB 1 1.5 NKTCL CR1 BEAM Alive with NED 34 nodes and splenomegaly 10 20/F Ovary, liver, spleen, BM and CNS IVB 3 75.0 DLBCL CR2 R-BEAM Alive with NED 29 aaIPI, age-adjusted international prognostic index; BM, bone marrow; OS, overall survival; APBSCT, autologous peripheral blood stem cell transplantation; CNS, central nervous system; B-LBL, B-cell lymphoblastic lymphoma; GZL, gray zone lymphoma; DLBCL, diffuse large B-cell lymphoma; T-LBL, T-cell lymphoblastic lymphoma; NKTCL, natural killer T-cell lymphoma; MALToma, mucosa- associated lymphoid tissue lymphoma; CR1, first complete remission; CR2, second complete remission; CRu, unconfirmed complete remission; PR, partial remission; R-BEAM, BEAM plus rituximab; NED, no evidence of disease; PD, progressive disease. 1827 1828 ONCOLOGY LETTERS 10: 1826-1830, 2015 (G-CSF; Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan). Periph- and BMB were normal. Ultrasound results were unremark- eral blood stem cells (PBSCs) were harvested using a standard able. A positron emission tomography-computed tomography procedure on a COBE spectra apheresis system (Terumo (PET-CT) scan revealed no evidence of a tumor. The child was BCT, Inc., Lakewood, CO, USA) 2-4 times. The cells were finally diagnosed as having primary thoracic vertebral B-LBL cryopreserved in -80˚C refrigerate (Sanyo Electric Co., Ltd., stage IVA with an age-adjusted international prognostic index Moriguchi, Japan). Cells were successfully collected from (aaIPI) of 2 and an Eastern Cooperative Oncology Group all patients. The median mononuclear cell dose infused was (ECOG) score of 2. Four months later, the patient underwent 7.8x10 8/kg (range, 6.61-12.38x108/kg) and the median CD34+ APBSCT. The conditioning regimen was BEAM plus ritux- cell dose infused was 4.81x106/kg (range, 1.09-12.13x106/kg). imab (R-BEAM). Twenty-nine months after APBSCT, she is Hematopoietic reconstitution was observed in all patients. The now well and in continuing complete remission (CCR). median time to neutrophil engraftment was 10 days (range, 8-14 days) and to platelet engraftment was 15 days (range, Case 2. An 11-year-old male sought care in an outside hospital 12-19 days). Following APBSCT, two patients with bulky with a 1-week history of abdominal pain. Ultrasound revealed mediastinal mass received local radiotherapy and one patient a mass in the right lower quadrant. Exploratory laparotomy was with central nervous system involvement received cranio- performed. A 5x5-cm mass was resected, and an ileocecos- spinal radiotherapy. Nine patients with CR1, CR2 and CRu tomy was carried out. Histopathological examination revealed survived with no evidence of disease. Only one patient with the aggregation of small atypical lymphoid cells. IHC staining + PR succumbed to progressive disease. revealed positivity for LCA, CD20 and CD79a, Ki67 40% , and negativity for CD3, CD5, CD23 and cyclin D1. The Conditioning regimen. Nine patients received the BEAM diagnosis was mucosa-associated lymphoid tissue lymphoma regimen (carmustin 300 mg/m2x1, day -6; etoposide 75 mg/m2, (MALToma). Q12hx4, days -5, -4, -3 and -2; cytarabine 100 mg/m2, Q12hx4, The patient was admitted to our hospital in September 2008 days -5, -4, -3 and -2; and melphalan 140 mg/m2x1, day -1). One for chemotherapy. Physical examination revealed a good state, patient received the modified BuCy regimen (hydroxyurea no superficial lymph node enlargement or hepatospleno- 2 g/m2, Q12hx2, days -9 and -8; cytarabine 2 g/m2x1, day -7; megaly. Laboratory tests revealed HGB 97 g/l, WBC 4.5x109/l, busulfan 1 mg/kg, Q6hx2, days -6 and -5; cyclophosphamide PLT 183x109/l and LDH 382 U/l. The liver and renal func- 1.8 g/m2x2, days -4 and -3; and lomustine 0.2 g/m2x1, day -2). tions, total protein levels, a coagulation test, and CSF, CMV Four patients received rituximab 375 mg/m2x2, days -1 and +8. and EBV tests were normal. A BM smear and BMB were normal. The CT scan revealed hilar liver lymphadenopathy Case 1. An 11-year-old female sought care at the Second and mild splenomegaly.
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