BackgroundIn spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML)-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs) or mesenchymal stromal cells rather than to hematopoietic cells.MethodsTo examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis.ResultsHPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3+ T-cell proliferation was suppressed in the presence of HPB-AML-I cells.ConclusionsWe conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells.
Background: As in LMICs, the prognosis of childhood ALL in Indonesia was lower than in HICs. Indonesian-ALL2013 protocol resulted in more toxicities and abandonments than expected. Therefore, it was modified into a pilot ALL2016 protocol. Changes to the ALL2013 protocol: no anthracyclines in SR, dexamethasone replaced prednisone in reinduction for HR and some drugs were rescheduled. Procedure: We compare the outcome of ALL2013 and ALL2016. Results: A total of 383 children with ALL were diagnosed, 21 were excluded. ALL2013 included 174 patients (106 SR and 68 HR) and ALL2016 188 (91 SR and 97 HR). The outcome of the ALL2016 was better than the ALL2013 (pOS 67.0% vs 60.3%; p=0.087 and pEFS 50.0% vs 37.9%; p=0.012) even when the number of HR patients was significantly higher in ALL2016 (51.6% vs 39.1%). The ALL2016 showed an early advantage for SR patients (pEFS 56.7% vs 47.2%; p=0.114 and pOS 74.4% vs 69.8%; p=0.298) due to the decrease of toxic deaths (10.4% vs 5.5%; p=0.211) however the number of late relapses were still high (19.5% vs 13.2%; p=0.282). In the HR group, both pEFS and pOS were significantly better in ALL2016 (pEFS 43.3% vs 23.5%; p=0.010 and pOS 59.8% vs 45.6%; p=0.036) due to less relapses (14.4% vs 29.4%; p=0.019). Both SR and HR showed a smaller number of abandonments in ALL2016. Conclusions: After small changes in protocol, initial toxicity and abandonments were reduced and the pOS and pEFS were improved. However, relapses still need to be lessened in the next protocol.
AIM: To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma. METHODS: This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr. Sardjito General Hospital, between 1st January 2014 and 31st December 2020. Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma. The subjects with lag time > one year were included in the case group, while the subjects with lag time < one year were included in the control group. RESULTS: The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma (P=0.005 and P=0.006, respectively). The lag time was also significantly correlated with both metastasis event [odds ratio (OR): 5.06, 95%Cl: 1.56-16.44, P=0.006] and mortality (OR: 4.54, 95%Cl: 1.37-15.07, P=0.011). The follow-up was continued for 32 subjects for 3y after initial diagnoses. Survival analysis revealed a significant difference among these two groups (P=0.021). Furthermore, lag time was significantly correlated with survival of retinoblastoma (r=-0.53, P=0.046). CONCLUSION: The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma. Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.
Background Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors. Methods A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML. Results Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. In a multivariate logistic regression analysis, compared with those of diagnostic white blood cell and peripheral blood myeloblast counts, treatment-related pneumonia, gastrointestinal tract infection, and sepsis were the most responsible factors for the occurrence of death within the first year of treatment [relative risk (RR), 2.82; 95% confidence interval (95% CI), 0.99–8.04; P = 0.05]. OS analysis showed that 43% and 16% of children with ALC0 of more than 4.5 × 109/L and less than 4.5 × 109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% CI, 0.33–1.18; P = 0.15]. Conclusion Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.
Background Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast, to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors. Methods A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML. Results Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. Of these 65 children, 56 (86%) children received Cytosine arabinoside in the first week of treatment (National Pilot Protocol and Pediatric AML Protocol), while 9 (14%) children did not (SIOP PODC Protocol with prephase). OS analysis showed that 44% and 19% of children with ALC0 of more than 4.5 × 109/L and ALC0 of less than 4.5×109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% confidence interval (95% CI), 0.33–1.18; P = 0.15]. Conclusion Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.
Sacrococcygeal yolk sac tumor (YST) is an infrequent extra-gonadal malignant germ cell tumor (GCT) that occurs exclusively within the first two years of life. A two-year-old girl came with a massive mass on her left buttock, which continued to grow, and within three months had become extremely large and hindered her from walking. Physical examination revealed a sacrococcygeal mass of 15 cm in diameter. Multislice CT showed an intraluminal inferior cava vein mass extending into the pelvic cavity with coccygeal osseous destruction, pulmonary metastasis, and multiple hepatic metastases. Laboratory data revealed elevated tumor marker values for alpha-feto-protein (AFP), lactate dehydrogenase (LDH), and Ca-125. Cytopathology following fine needle aspiration biopsy evaluation of the smear sample revealed a cellular tumor with pseudo glandular, microcystic, and solid patterns. The cytopathology did not show pathognomic findings. An immunocytochemistry (IHC) examination of the cell block showed a positive result for anti-AFP antibody. The patient was diagnosed and treated with chemotherapy for a sacrococcygeal YST. Clinical follow-up on the fourth month showed that the tumor had shrunk to 4 cm in size. Laboratory follow-up data after four months showed significant improvement. Unfortunately, the patient passed away on the seventh cycle of chemotherapy due to lung and hepatic metastases.
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