Infectious complications in children treated for hodgkin and non-hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology

Abstract Introduction: Recently, early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was identified as a subtype of T-cell ALL (T-ALL), with distinctive gene expression and cell marker profiles. Some reports revealed that ETP-ALL was associated with a high risk of remission induction failure and relapse. In precursor T-cell lymphoblastic lymphoma (T-LBL), the clinical features and prognosis of the ETP subtype are not clear yet. In this study, we analyzed the data obtained from patients of advanced stage T-LBL to clarify the prognosis of pediatric T-LBL according to the immunophenotypes, including the ETP subtype of LBL. Patients and methods: From November 2004 to October 2010, 136 children (aged 1–18 years) with newly diagnosed advanced stage LBL (stages III and IV) were eligible for the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 study. We analyzed their immunophenotyping data as well as the ETP subtype. The immunophenotype of T-LBL was classified into pro-T, pre-T, intermediate T, and mature T based on the European Group for the Immunological Characterization of Leukemias (EGIL) classification. The definition of ETP subtype LBL was based on a previous report from the Tokyo Children’s Cancer Study Group (Inukai et al, 2011) using a scoring system consisting of the following 11 markers: CD4, CD8, CD13, CD33, CD34, HLA-DR, CD2, CD3, CD4, CD10, and CD56. Both definitions were based on flow cytometric analysis. Results: In this analysis, 104 (76%) patients were diagnosed with T-LBL. Sufficient data to evaluate the EGIL classification was available for 40 out of 104 patients. The remaining patients could not be classified due to incomplete immunophenotypic data. There were 1, 9, 21, and 9 cases of Pro-T, pre-T, intermediate T, and mature T, respectively. The 3-year event-free survival (EFS) of pro-T/pre-T and intermediate T/mature T was 80.0 ± 12.7% and 76.7 ± 7.7%, respectively (P = 0.7586). For evaluating the ETP subtype of LBL, sufficient data, obtained by using the scoring system with 11 markers, was available for 40 patients. Eight (20%) and 32 (80%) patients were classified as having ETP and non-ETP subtype, respectively. Bone marrow involvement for patients with ETP and non-ETP subtype was observed in 7 (88%) and 11 (34%) cases, respectively (P = 0.014). Central nervous system involvement in patients with ETP and non-ETP subtype was observed in 2 (25%) and 0 cases, respectively (P = 0.036). Thus, stage IV classification was more frequently observed in patients with ETP subtype than in patients with non-ETP subtype (P = 0.014). The 3-year EFS of patients with ETP and non-ETP subtype were 75.0 ± 15.3% and 71.9 ± 8.0%, respectively. There was no significant difference in EFS between patients with ETP and non-ETP subtype (P = 0.8281). Conclusion: For 40 out of 104 T-LBL patients, sufficient data was available to evaluate the immunophenotype for EGIL classification and ETP subtype. There was no significant difference in EFS according to the immunophenotypic subtype of T-LBL. In contrast to T-ALL, ETP subtype in LBL was not statistically related to EFS in this analysis. Disclosures No relevant conflicts of interest to declare.

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Prospective Study of 168 Infants with Transient Abnormal Myelopoiesis with Down Syndrome: Japan Pediatric Leukemia/Lymphoma Study Group, TAM-10 Study

Blood ◽

10.1182/blood.v126.23.1311.1311 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1311-1311 ◽

Cited By ~ 4

Author(s):

Hideki Muramatsu ◽

Tomoyuki Watanabe ◽

Daisuke Hasegawa ◽

Park Myoung-ja ◽

Shotaro Iwamoto ◽

...

Keyword(s):

Risk Factors ◽

Down Syndrome ◽

Gestational Age ◽

Early Death ◽

Study Group ◽

Pediatric Leukemia ◽

Factors Associated ◽

Transient Abnormal Myelopoiesis ◽

Lymphoma Study Group ◽

Wbc Count

Abstract Introduction: Transient abnormal myelopoiesis (TAM) occurs in approximately 10% of infants with Down syndrome (DS). Although most patients achieve spontaneous remission, some develop severe organ failure and die in their infancy. Previous studies have identified several risk factors associated with early death in such cases, including a high white blood cell (WBC) count, early gestational age, and ascites (Massey GV, 2006; Muramatsu H, 2008; Klusmann JH, 2008). Although chemotherapy with low-dose cytosine arabinoside (LDCA) has been applied for severe cases, its side effect profile has not been fully demonstrated in an adequate number of patients. Here we prospectively analyzed 168 infants with DS who were diagnosed with TAM, including 52 patients treated with LDCA. We assessed the efficacy and safety of LDCA therapy in these cases. Patient and Methods: Between May 2011 and February 2014, 168 infants (90 boys and 78 girls) were diagnosed with TAM and prospectively registered in the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) TAM-10 study. GATA1 gene mutations were identified in all except 7 patients who had a very low blast percentage. The median (range) of WBC count was 38.6 (2.4-478.7) × 109 cells/L, and the median (range) of gestational age was 37 (29-40) weeks. Thirty one (18%) patients developed anasarca at diagnosis, and 23 (14%) patients developed acute megakaryocytic leukemia. Results: The overall survival (OS) rate and the event-free survival (EFS) rate at 1 year from diagnosis [95% confidential interval (CI)] were 86.3% (80.1-90.7), and 80.2% (73.2-85.5), respectively. Univariate analysis identified the following covariates as risk factors associated with early death (<9 months): early gestational age [<37 weeks; hazard ratio (HR; 95% CI) = 4.482 (1.826-10.997), p = 0.001], parenchymal bleeding [HR (95% CI) = 5.746 (2.241-14.734), p < 0.001], anasarca [HR (95% CI) = 13.344 (5.419-32.860), p < 0.001], and high WBC count [ ≥100 × 109 cells/L; HR (95% CI) = 8.013 (3.354-19.144), p < 0.001]. The multivariate Cox hazard model identified anasarca and a high WBC count (≥100 × 109 cells/L) as independent risk factors for early death. With regard to the 52 patients who received LDCA therapy, only anasarca remained an independent risk factor for early death. Subgroup analysis in patients with a high WBC count (≥100 × 109 cells/L; n = 36) showed that LDCA therapy significantly improved survival [1-year OS (95% CI) = 78.3% (55.4-90.3; n = 23) vs. 38.5% (14.1-62.8; n = 13); p = 0.009]. In contrast, the survival rate of patients with anasarca (n = 31) did not improve on receiving LDCA therapy [1-year OS (95% CI) = 58.3% (27.0-80.1; n = 12) vs. 47.4% (24.4-67.3; n = 19); p = 0.525]. The most common side effect of LDCA was neutropenia (grade 3-4 = 59%), and one patient died due to tumor lysis syndrome. Conclusion: This prospective study confirmed that a high WBC count and anasarca are risk factors for early death in patients with DS who were diagnosed with TAM. Although LDCA therapy could significantly improve the survival rate in patients with a high WBC count, it failed to change the prognosis of patients with anasarca. A new treatment modality is required for most severe TAM patients with anasarca at diagnosis. Disclosures No relevant conflicts of interest to declare.

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Randomized study of granulocyte colony stimulating factor for childhood B-cell non-Hodgkin lymphoma: a report from the Japanese pediatric leukemia/lymphoma study group B-NHL03 study

Leukemia & Lymphoma ◽

10.3109/10428194.2015.1106534 ◽

2015 ◽

Vol 57 (7) ◽

pp. 1657-1664 ◽

Cited By ~ 3

Author(s):

Masahito Tsurusawa ◽

Tomoyuki Watanabe ◽

Masahiko Gosho ◽

Tetsuya Mori ◽

Tetsuo Mitsui ◽

...

Keyword(s):

B Cell ◽

Randomized Study ◽

Study Group ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Pediatric Leukemia ◽

Non Hodgkin Lymphoma ◽

Lymphoma Study Group ◽

Group B ◽

Stimulating Factor

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The outcomes of relapsed acute myeloid leukemia in children: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05R study

10.22541/au.159586058.80128116 ◽

2020 ◽

Author(s):

Hiroshi Moritake ◽

Shiro Tanaka ◽

Takako Miyamura ◽

Hideki Nakayama ◽

Norio Shiba ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Study Group ◽

Pediatric Leukemia ◽

Lymphoma Study Group ◽

Leukemia In Children ◽

Relapsed Acute Myeloid Leukemia ◽

Acute Myeloid

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Nation-Wide Survey of Relapsed Infantile Acute Lymphoblastic Leukemia In Japan: Treatment and Outcome From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) MLL03 Study.

Blood ◽

10.1182/blood.v116.21.1025.1025 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1025-1025

Author(s):

Takako Miyamura ◽

Katsuyoshi Koh ◽

Daisuke Tomizawa ◽

Takashi Sato ◽

Koji Kato ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Relapse Rate ◽

Treatment Strategy ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Conditioning Regimen ◽

Study Group ◽

Pediatric Leukemia ◽

The Future ◽

Lymphoma Study Group

Abstract Abstract 1025 Introduction: Infantile acute lymphoblastic leukemia (ALL) is a rare leukemia subtype in infants with poor prognosis. Its outcome has gradually improved due to the development of treatment, including intensive chemotherapy or hematopoietic stem cell transplantation (SCT). However, prognosis of relapsed patients is extremely poor, which prompt us to establish the new treatment strategy for them. To establish the future treatment strategy for the relapsed cases, we here investigated the incidence of relapse, treatment, prognosis, and possible risk factors of relapsed cases with infantile ALL treated by the Japanese Pediatric Leukemia /Lymphoma Study Group (JPLSG) MLL03 study. Subjects: All relapsed cases with infantile ALL who underwent the MLL03 study between April 2004 and June 2009 were eligible for the study. The questionnaires were sent to all participants, asking the relapsed patients with infantile ALL by the MLL03 study. The questionnaires consisted of the time and site of relapse, treatment after relapse, presence or absence of remission prior to the second SCT, conditioning regimen for the second SCT, and age, white blood cell count, and presence or absence of central nervous system (CNS) infiltration at initial onset. Results: Total 63 patients were treated in this study period (mean follow-up, 31.8 months). Among them, 24 patients relapsed at any site after first complete remission (38%). These include 7 boys and 17 girls. Age at onset was less than 6 months in 19, and 6–12 months in 5. The overall survival (OS) rate of 24 patients was 60.2 ± 11.1% at 3 years; 44.6 ± 12.7% at 4 years, and 23.5 ± 13.4% at 5 years. Twenty-one of 24 patients (87.5%) relapsed after initial SCT; only three patients (12.5%) relapsed before SCT. Two patients relapsed early within 6 months after initial treatment terminally died. All four patients who relapsed at extramedullary site except CNS have survived, suggesting better prognosis. Patients diagnosed at age of less than 6 months also showed poor prognosis after relapse (5 year OS rate was 14.9 ± 13.0%). Presence or absence of remission prior to the second SCT was not a significant prognostic factor (28.3 ± 21.8% versus 15.6 ± 14.2%). Discussion: In the JPLSG MLL03 study, 38% of patients with infantile ALL relapsed. Only four patients relapsed prior to the initial SCT, indicating that the aim of the MLL03 study, to reduce the early relapse rate by performing the early SCT, could have been achieved. On the other hand, 87.5% of the patients relapsed after initial SCT in this study. Most of them were less than 6 months at onset. Several reasons for the high relapse rate after SCT should be considered, which include low graft-versus-leukemia (GVL) effect for infantile ALL, remained minimal residual disease (MRD) before SCT, or inappropriate conditioning regimen in this study. Since we have analyzed MRD before and after SCT in each patient treated by the MLL03 study, one reason could be resolved. In addition, the treatment strategy to induce GVL effect for infantile ALL should be established and we should reconsider the treatment strategy. Finally, appropriate treatment strategy for relapsed cases should be organized in the future. Disclosures: No relevant conflicts of interest to declare.

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Effectiveness of Intrathecal Liposomal Cytarabine in Treatment of Childhood Hematopoietic Malignancies – Experience of Polish Pediatric Leukemia/Lymphoma Study Group

Blood ◽

10.1182/blood.v118.21.4240.4240 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4240-4240

Author(s):

Tomasz Szczepanski ◽

Lidia Kajdas ◽

Aneta Pobudejska-Pieniazek ◽

Ninela Irga ◽

Maciej Niedzwiecki ◽

...

Keyword(s):

Acute Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Study Group ◽

Liposomal Cytarabine ◽

Pediatric Leukemia ◽

Cns Disease ◽

Hematopoietic Malignancies ◽

Lymphoma Study Group ◽

Hodgkin's Lymphomas

Abstract Abstract 4240 Introduction: Liposomal Cytarabine for intrathecal administration is characterized by prolonged activity and better penetration to central nervous system (CNS). This makes it promising medicine for treating children with hematopoietic malignancies relapsing in CNS or refractory CNS disease. The purpose of the Study: The study aimed at retrospective evaluation of the effectiveness of liposomal Cytarabine (Depocyte®) administrated intrathecally as a part of the treatment of hematopoietic malignancies in Polish children. Patients and methods: The study group consisted of 23 patients, 11 boys and 12 girls, treated in the centers of Polish Pediatric Leukemia/Lymphoma Study Group, including 18 patients with acute lymphoblastic leukemia (ALL), 3 patients with acute myeloid leukemia (AML) and two children with high grade Non-Hodgkin’s Lymphomas (NHL). The median age of the children was 10.8 years (range: 1.3 to 18 years). Liposomal cytarabine treatment was administered on compassionate basis to 20 children with relapsed acute leukemia / NHL, a single child with secondary leukemia, one patient with severe neurotoxicity after intrathecal Methotrexate during front-line treatment and in one child with large granulocytic sarcoma, penetrating into CNS. Thirteen patients received liposomal cytarabine dosage of 50 mg, while the remaining 10 children were exposed to the doses of 25–35 mg, all in association with prophylactic dexamethasone administration. The number of liposomal Cytarabine injections ranged from 1 to 11, mean 5 doses per patient. Results: The clearance of CNS disease was achieved in 15 of 23 patients (65%). Eight children were alive during the follow-up procedure, including 3 patients in complete remission after treatment completion. Grade IV neurotoxicity was observed in five children, which might be also partly related to CNS malignancy. Another side effects occurred in 4 patients, including headache, vertigo, paresthesias and seizures. Conclusion: Liposomal cytarabine administered intrathecally is effective treatment for CNS disease in children with relapsed acute leukemia/NHL with acceptable toxicity profile. Disclosures: No relevant conflicts of interest to declare.

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