Symptom Interval and Patient Delay Affect Survival Outcomes in Adolescent Cancer Patients

PURPOSE: Unique features of adolescent cancer patients include cancer types, developmental stages, and psychosocial issues. In this study, we evaluated the relationship between diagnostic delay and survival to improve adolescent cancer care. MATERIALS AND METHODS: A total of 592 patients aged 0-18 years with eight common cancers were grouped according to age (adolescents, ≥10 years; children, <10 years). We retrospectively reviewed their symptom intervals (SIs, between first symptom/sign of disease and diagnosis), patient delay (PD, between first symptom/sign of disease and first contact with a physician), patient delay proportion (PDP), and overall survival (OS). RESULTS: Mean SI was significantly longer in adolescents than in children (66.4 days vs. 28.4 days; p<0.001), and OS rates were higher in patients with longer SIs (p=0.001). In children with long SIs, OS did not differ according to PDP (p=0.753). In adolescents with long SIs, OS was worse when PDP was ≥0.6 (67.2%) than <0.6 (95.5%, p=0.007). In a multivariate analysis, adolescents in the long SI/PDP ≥0.6 group tended to have a higher hazard ratio (HR, 6.483; p=0.069) than those in the long SI/PDP <0.6 group (HR=1, reference). CONCLUSION: Adolescents with a long SI/PDP ≥0.6 had lower survival rates than those with a short SI/all PDP or a long SI/PDP <0.6. They should be encouraged to seek prompt medical assistance by a physician or oncologist to lessen PDs.

Subclinical Hypothyroidism in Childhood Cancer Survivors

PURPOSE: In childhood cancer survivors, the most common late effect is thyroid dysfunction, most notably subclinical hypothyroidism (SCH). Our study evaluated the risk factors for persistent SCH in survivors. MATERIALS AND METHODS: Survivors (n=423) were defined as patients who survived at least 2 years after cancer treatment completion. Thyroid function was assessed at this time and several years thereafter. Two groups of survivors with SCH were compared: those who regained normal thyroid function during the follow-up period (normalized group) and those who did not (persistent group). RESULTS: Overall, 104 of the 423 survivors had SCH. SCH was observed in 26% of brain or nasopharyngeal cancer survivors (11 of 43) and 21.6% of leukemia survivors (35 of 162). Sixty-two survivors regained normal thyroid function, 30 remained as persistent SCH, and 12 were lost to follow-up. The follow-up duration was 4.03 (2.15-5.78) years. Brain or nasopharyngeal cancer and Hodgkin disease were more common in the persistent group than in the normalized group (p=0.002). More patients in the persistent group received radiation (p=0.008). Radiation to the head region was higher in this group (2394±2469 cGy) than in the normalized group (894±1591 cGy; p=0.003). On multivariable analysis, lymphoma (p=0.011), brain or nasopharyngeal cancer (p=0.039), and head radiation dose ≥1800 cGy (p=0.039) were significant risk factors for persistent SCH. CONCLUSION: SCH was common in childhood cancer survivors. Brain or nasopharyngeal cancer, lymphoma, and head radiation ≥1800 cGy were significant risk factors for persistent SCH.

Etiologies and characteristics of children with chief complaint of short stature

PURPOSE: Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature. METHODS: We retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed. RESULTS: Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%). CONCLUSION: A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.

Prevalence and Clinical Implication of Partial Tandem Duplication of the Mixed Lineage Leukemia Gene in Pediatric Acute Leukemia / 임상소아혈액종양

BACKGROUND: The mixed lineage leukemia (MLL) gene may induce hematopoiesis and leukemia. Partial tandem duplication of MLL (MLL-PTD) is associated with poor prognosis in acute myeloid leukemia (AML); however, the significance of MLL-PTD in acute lymphoblastic leukemia (ALL) has not been thoroughly studied. We evaluated the incidence, relationship with other cytogenetic abnormalities, and the prognostic role of MLL-PTD in ALL.METHODS: We reviewed medical records from pediatric patients diagnosed with ALL in Severance Hospital, Yonsei University Health System, South Korea from 2002 to 2008. MLL-PTD was detected by nested reverse transcriptase polymerase chain reaction.RESULTS: In ALL patients, 50.0% (42/84) were positive for MLL-PTD. There was no significant difference in the 10-year overall survival (10Y OS) and event-free survival (EFS) between MLL-PTD-positive (+) and MLL-PTD-negative (-) groups (69.4% vs. 76.2%, P=0.609, and 62.6% vs. 66.7%, P=0.818, respectively). The combination of high level of lactate dehydrogenase (>1,100 IU/L) and MLL-PTD(+) [MLL-PTD(+)/High LDH] was a statistically significant negative prognostic factor for 10Y OS and EFS (P=0.0226 and P=0.0230, respectively). In multivariate analysis, National Cancer Institute risk stratification and very high risk features were independent significant prognostic factors but MLL-PTD (+)/High LDH was not.CONCLUSION: MLL-PTD was observed frequently in pediatric ALL patients. MLL-PTD was not an independent prognostic factor. MLL-PTD (+)/High LDH should be evaluated further for its prognostic potential in ALL.

Radiation or Chemotherapy rather than Observation may be a Better Modality after Subtotal Resection for Pilocytic Astrocytoma in Children / 임상소아혈액종양

BACKGROUND: Pilocytic astrocytoma (PA) is a low-grade glioma that occurs primarily in children and young adults. The optimal postoperative treatment modality after subtotal resection (STR) of PAs remains to be elucidated. The aim of this study was to compare the efficacies of different post-STR treatment modalities and to examine the risk factors for the progression of PAs.METHODS: We reviewed the medical records of 91 pediatric PA patients in a single institute during a 30-year period. Kaplan-Meier analysis was used to assess overall survival (OS) and progression-free survival (PFS), and Cox proportional hazard models were used to calculate hazard ratios.RESULTS: The median age of 91 patients was 8.9 years (range, 0.3-17.9). GTR was perfomed, whenever possible. Patients who underwent STR afterwards received either radiotherapy, chemotherapy, or were observed without further treatment, according to clinician preference. In total group, 10-year OS was 97.4% and 10-year PFS was 57.2%. In GTR group (N=33), 10-year OS and PFS was 100%. In STR group (N=49), 10-year OS was 97.7%, while 10-year PFS was 38.6%. STR group underwent following postoperative (PO) modalities; observation (PO-Obs, N=32), radiotherapy (PO-RT, N=10), chemotherapy (PO-CTx, N=7). The 10-year PFS rate was higher in patients who received postoperative treatment (either PO-RT or PO-CTx) than in patients who received PO-Obs (62.5% vs 27.0%, P=0.039). In multivariate analysis for STR group, PO-CTx (Hazard ratio (HR)=0.20, P=0.035) and PO-RTx (HR=0.13, P=0.008) were superior to observation, respectively.CONCLUSION: Radiation and chemotherapy are better post-STR treatment modalities than observation for pediatric PA patients.

Lower Diagnostic Value of Bone Marrow Biopsy in Children with Fever of an Unknown Origin / 임상소아혈액종양

BACKGROUND: Diagnostic value of Bone marrow (BM) biopsies for fever of unknown origin (FUO) remain controversial and BM biopsies are difficult to perform in young patients. Our study aimed to elucidate the diagnostic yield of BM biopsies in FUO patients of all age, particularly for diagnosing hematological malignant diseases.METHODS: The medical records of 150 patients, hospitalized between January 1, 2008 and June 30, 2013, who underwent BM biopsies were evaluated to determine the cause of FUO. FUO was defined as fever (38.3degrees C, 101) either on several occasions during the 3 hospital days without a clear cause, after 1 week of invasive investigation, or after 3 outpatient visits. BM-specific diagnoses included those determined by BM biopsies (i.e., leukemia, lymphoma, myeloproliferative disease, myelodysplastic syndrome, aplastic anemia, and hemophagocytic lymphohistiocytosis).RESULTS: The final diagnoses of 24 patients (16%) were determined by BM biopsies; the majority included hematologic diseases and malignant neoplasms. Low hemoglobin levels, thrombocytopenia, bicytopenia, increased Lactate dehydrogenase (LDH) and ferritin levels, and ultrasonographic/computed tomographic abnormalities were significant risk factors (P<0.05). The young patient group (<18 years old) was safer from the tendency of BM biopsy diagnosis compared to adult patient group (>40 years old).CONCLUSION: Some laboratory abnormalities were related to the BM biopsy diagnostic yield. Furthermore, pediatric age was an important factor for deciding to do not perform excessive BM biopsies in FUO cases.

Prevalence and Clinical Implication of Partial Tandem Duplication of the Mixed Lineage Leukemia Gene in Pediatric Acute Leukemia / 임상소아혈액종양

BACKGROUND: The mixed lineage leukemia (MLL) gene may induce hematopoiesis and leukemia. Partial tandem duplication of MLL (MLL-PTD) is associated with poor prognosis in acute myeloid leukemia (AML); however, the significance of MLL-PTD in acute lymphoblastic leukemia (ALL) has not been thoroughly studied. We evaluated the incidence, relationship with other cytogenetic abnormalities, and the prognostic role of MLL-PTD in ALL. METHODS: We reviewed medical records from pediatric patients diagnosed with ALL in Severance Hospital, Yonsei University Health System, South Korea from 2002 to 2008. MLL-PTD was detected by nested reverse transcriptase polymerase chain reaction. RESULTS: In ALL patients, 50.0% (42/84) were positive for MLL-PTD. There was no significant difference in the 10-year overall survival (10Y OS) and event-free survival (EFS) between MLL-PTD-positive (+) and MLL-PTD-negative (-) groups (69.4% vs. 76.2%, P=0.609, and 62.6% vs. 66.7%, P=0.818, respectively). The combination of high level of lactate dehydrogenase (>1,100 IU/L) and MLL-PTD(+) [MLL-PTD(+)/High LDH] was a statistically significant negative prognostic factor for 10Y OS and EFS (P=0.0226 and P=0.0230, respectively). In multivariate analysis, National Cancer Institute risk stratification and very high risk features were independent significant prognostic factors but MLL-PTD (+)/High LDH was not. CONCLUSION: MLL-PTD was observed frequently in pediatric ALL patients. MLL-PTD was not an independent prognostic factor. MLL-PTD (+)/High LDH should be evaluated further for its prognostic potential in ALL.

Radiation or Chemotherapy rather than Observation may be a Better Modality after Subtotal Resection for Pilocytic Astrocytoma in Children / 임상소아혈액종양

BACKGROUND: Pilocytic astrocytoma (PA) is a low-grade glioma that occurs primarily in children and young adults. The optimal postoperative treatment modality after subtotal resection (STR) of PAs remains to be elucidated. The aim of this study was to compare the efficacies of different post-STR treatment modalities and to examine the risk factors for the progression of PAs. METHODS: We reviewed the medical records of 91 pediatric PA patients in a single institute during a 30-year period. Kaplan-Meier analysis was used to assess overall survival (OS) and progression-free survival (PFS), and Cox proportional hazard models were used to calculate hazard ratios. RESULTS: The median age of 91 patients was 8.9 years (range, 0.3-17.9). GTR was perfomed, whenever possible. Patients who underwent STR afterwards received either radiotherapy, chemotherapy, or were observed without further treatment, according to clinician preference. In total group, 10-year OS was 97.4% and 10-year PFS was 57.2%. In GTR group (N=33), 10-year OS and PFS was 100%. In STR group (N=49), 10-year OS was 97.7%, while 10-year PFS was 38.6%. STR group underwent following postoperative (PO) modalities; observation (PO-Obs, N=32), radiotherapy (PO-RT, N=10), chemotherapy (PO-CTx, N=7). The 10-year PFS rate was higher in patients who received postoperative treatment (either PO-RT or PO-CTx) than in patients who received PO-Obs (62.5% vs 27.0%, P=0.039). In multivariate analysis for STR group, PO-CTx (Hazard ratio (HR)=0.20, P=0.035) and PO-RTx (HR=0.13, P=0.008) were superior to observation, respectively. CONCLUSION: Radiation and chemotherapy are better post-STR treatment modalities than observation for pediatric PA patients.

Lower Diagnostic Value of Bone Marrow Biopsy in Children with Fever of an Unknown Origin / 임상소아혈액종양

BACKGROUND: Diagnostic value of Bone marrow (BM) biopsies for fever of unknown origin (FUO) remain controversial and BM biopsies are difficult to perform in young patients. Our study aimed to elucidate the diagnostic yield of BM biopsies in FUO patients of all age, particularly for diagnosing hematological malignant diseases. METHODS: The medical records of 150 patients, hospitalized between January 1, 2008 and June 30, 2013, who underwent BM biopsies were evaluated to determine the cause of FUO. FUO was defined as fever (38.3degrees C, 101) either on several occasions during the 3 hospital days without a clear cause, after 1 week of invasive investigation, or after 3 outpatient visits. BM-specific diagnoses included those determined by BM biopsies (i.e., leukemia, lymphoma, myeloproliferative disease, myelodysplastic syndrome, aplastic anemia, and hemophagocytic lymphohistiocytosis). RESULTS: The final diagnoses of 24 patients (16%) were determined by BM biopsies; the majority included hematologic diseases and malignant neoplasms. Low hemoglobin levels, thrombocytopenia, bicytopenia, increased Lactate dehydrogenase (LDH) and ferritin levels, and ultrasonographic/computed tomographic abnormalities were significant risk factors (P40 years old). CONCLUSION: Some laboratory abnormalities were related to the BM biopsy diagnostic yield. Furthermore, pediatric age was an important factor for deciding to do not perform excessive BM biopsies in FUO cases.

Successful Selective CD34+ Cell Infusion after Late Graft Failure of Hematopoietic Stem Cell Transplantation in Two Cases of Severe Aplastic Anemia / 임상소아혈액종양

Matched sibling bone marrow transplantation (BMT) in severe aplastic anemia (SAA) has been known as the treatment of choice in children and young adults. To overcome graft failure, second stem cell transplantation showed good results in previous studies. Here we report two cases of aplastic anemia patients with late graft failure and resulted in successful complete recovery after selective CD34+ cell boost infusion. The patients previously underwent allogeneic BMT from HLA-matched sibling donors and the engraftment was achieved although their CBC started to decrease respectively 3 months and 11 months after transplantation. Both patients received selective CD34+ cell infusion without additional conditioning therapy. Their CBC showed significant improvement and they are doing well without transfusion or complications. From this study we suggest that selected CD34+ cell boost treatment can be a promising curative treatment for late graft failure after matched sibling BMT in SAA patients.

Successful Selective CD34+ Cell Infusion after Late Graft Failure of Hematopoietic Stem Cell Transplantation in Two Cases of Severe Aplastic Anemia / 임상소아혈액종양

Matched sibling bone marrow transplantation (BMT) in severe aplastic anemia (SAA) has been known as the treatment of choice in children and young adults. To overcome graft failure, second stem cell transplantation showed good results in previous studies. Here we report two cases of aplastic anemia patients with late graft failure and resulted in successful complete recovery after selective CD34+ cell boost infusion. The patients previously underwent allogeneic BMT from HLA-matched sibling donors and the engraftment was achieved although their CBC started to decrease respectively 3 months and 11 months after transplantation. Both patients received selective CD34+ cell infusion without additional conditioning therapy. Their CBC showed significant improvement and they are doing well without transfusion or complications. From this study we suggest that selected CD34+ cell boost treatment can be a promising curative treatment for late graft failure after matched sibling BMT in SAA patients.

Successful Selective CD34+ Cell Infusion after Late Graft Failure of Hematopoietic Stem Cell Transplantation in Two Cases of Severe Aplastic Anemia / 임상소아혈액종양

Matched sibling bone marrow transplantation (BMT) in severe aplastic anemia (SAA) has been known as the treatment of choice in children and young adults. To overcome graft failure, second stem cell transplantation showed good results in previous studies. Here we report two cases of aplastic anemia patients with late graft failure and resulted in successful complete recovery after selective CD34+ cell boost infusion. The patients previously underwent allogeneic BMT from HLA-matched sibling donors and the engraftment was achieved although their CBC started to decrease respectively 3 months and 11 months after transplantation. Both patients received selective CD34+ cell infusion without additional conditioning therapy. Their CBC showed significant improvement and they are doing well without transfusion or complications. From this study we suggest that selected CD34+ cell boost treatment can be a promising curative treatment for late graft failure after matched sibling BMT in SAA patients.