Improvement of survival after hematopoietic stem cell transplantation and trends at a pediatric transplantation center; a three-decade journey.

BACKGROUND: Advances in stem cell transplantation have resulted in improved outcomes. METHODS: This is a retrospective study aimed to analyze changes in patient profile, transplantation, graft characteristics, and outcome among 241 pediatric patients who received stem cell transplantation in a single center between 1993 and 2019. RESULTS: In the 2010-2019, compared with the 1993-2009 period, a significantly higher 5-year overall survival (60% vs. 44%, p = .022) and an event-free survival (53% vs. 34%, p = .025) were observed. Cumulative incidence of deaths due to relapse or progression between the 1993-2009 and 2010-2019 periods were 33% and 26% respectively (p = .66). Cumulative incidence of non-relapse mortality was significantly higher during the 1993-2009 period compared with the 2010-2019 period for malignant diseases (57.7% vs. 28.3%, p = .007). The overall survival from acute graft-versus-host disease between 1993 and 2009 was 11% versus 46% between 2010 and 2019 (p = .0001). The overall survival from infection in both eras did not show any difference (p = .41). CONCLUSIONS: Development in transplantation technology has led to a decrease in non-relapse mortality and better control of graft-versus-host disease. However, relapse and infection remained as major causes of death. Studies evaluating institutional trends in patients undergoing HSCT and analyzing their mortality profile, can improve the management of patients, leading to a reduction in transplant-related problems.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Nimotuzumab-vinorelbine combination therapy versus other regimens in the treatment of pediatric diffuse intrinsic pontine glioma.

PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months. CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.

Associations between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and prognosis in patients with neuroblastoma.

OBJECTIVES: Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) is a new inflammatory marker that is effective in determining the prognosis of many solid tumors, chemotherapy responses, survival, and their recurrence rate. Therefore, we performed a retrospective study to investigate the effect of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio (PLR) on risk factors and prognosis in these patients. MATERIALS AND METHODS: In this study, 246 pediatric patients with neuroblastoma who were diagnosed, treated, and followed up during 2000-2021 in Division of Pediatric Oncology, Çukurova University Faculty of Medicine, were included. Required information of patients was obtained from archive files, Mergentech hospital program, and E-pulse system. RESULTS: Median value for NLR was found to be 1.06, for PLR it was found as 92. The relationship of NLR values with age, stage, risk group, and Shimada was found to be statistically significant with p < .001, vanillylmandelic acid (VMA) (p = .006) also depicted the significant value. Likewise, the relationship of PLR values with age (p < .001), stage (p = .022), Shimada (p = .004), and N-Myc amplification (p = .039) was found to be statistically significant as well. Survival analysis showed that no statistically significant difference was observed among the higher and lower values of NLR. Survival rates were noticed to be higher in the lower values of NLR (10-year overall survival [OS] 55% vs. 49%, 10-year event-free survival (EFS) 54% vs. 43%), albeit nonsignificant. CONCLUSION: Pretreatment evaluation of NLR and PLR values in patients with neuroblastoma may be instructive in respect of prognosis and risk group.

Pediatric posterior reversible encephalopathy syndrome: Age related clinico-radiological profile and neurologic outcomes.

BACKGROUND: The aim of this study was to analyze the characteristics of pediatric posterior reversible encephalopathy syndrome (PRES) to determine clinical and radiologic differences between younger and older age groups, and to identify risk factors for development of any neurologic sequelae. METHODS: The study cohort consisted of confirmed pediatric PRES patients in a tertiary care university hospital from January, 2015, to December, 2020. Demographic and clinical properties, radiological manifestations, and neurologic outcomes were noted. Children aged ≤6 years were compared with those older than 6 years and factors affecting neurologic outcomes were evaluated. RESULTS: The most common underlying diseases were oncological (37%) and kidney diseases (29%). Epileptic seizures were the most frequent symptoms at initial clinical presentation. The regions in the brain that were most commonly involved were the occipital region (n = 65, 96%), the parietal region (n = 52, 77%), and the frontal lobe (n = 35, 54%). Magnetic resonance imaging (MRI) findings were consistent with atypical patterns in most of the study cohort (71%). Patients with unfavorable clinical outcomes (n = 13, 19.1%) had longer initial seizure times and longer encephalopathy times, lower leucocyte and absolute neutrophil counts, and lower neutrophil to lymphocyte ratios. No relationship was found between MRI findings, involvement patterns, and neurologic outcomes. CONCLUSIONS: No clinically specific differences between two different age groups were found. Atypical imaging manifestations of pediatric PRES in our study had an incidence that was as high as those found in earlier adult studies. Multivariate logistic regression analysis showed that the initial neutrophil to lymphocyte ratio, absolute neutrophil counts, and white cell counts could not predict poor neurologic outcomes.

Total nucleated cell dose in graft is a better prognostic factor for survival in pediatric patients transplanted with bone marrow compared to CD34+, CD3+, or total mononuclear cell count.

BACKGROUND: Most studies investigating the impact of graft composition on transplant-related outcomes have focused on the effect of CD34+ cell dose and reported equivocal results. The aim of this study is to investigate the impact of doses of total nucleated cells (TNCs), total mononuclear cells (TMCs), CD3+, and CD34+ cells on the outcome of children receiving allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Children and adolescents who underwent allogeneic HSCT for malignant hemato-oncological diseases or nonmalignant diseases in Cukurova University Faculty of Medicine, Pediatric Bone Marrow Transplantation Center between 2010 and 2020 were enrolled in the study. RESULTS: A total of 212 patients receiving allogeneic HSCT (154 bone marrow transplantation; 58 peripheral blood stem cell transplantation) from matched related or unrelated donors were included in the study. Higher TNC doses associated with a superior 5-year event-free survival (EFS; 67.7% vs 44.7%) in the whole group (log-rank P = .027). Overall survival (OS) and EFS of bone marrow-transplanted patients differed significantly according to TNC doses (log-rank P = .041 and .027, respectively). Multivariant analysis for OS revealed a P value of .038 for TNC, Exp(B) = 1.939 (95% CI: [1.038, 3.621]). That for EFS revealed a P value of .025 for TNC, Exp(B) = 1.992 (95% CI: [1.088, 3.647]). There was no relationship between doses of CD34+ cells, CD3+ cells, TMC, TNC, and neutrophil or platelet engraftment. CONCLUSION: Our data suggest that TNC dose is a better prognostic factor for pediatric allogeneic HSCT outcomes than doses of CD34+ cells, CD3+ cells, or TMC in patients transplanted with bone marrow. Future studies analyzing cell subsets and other components in TNC could elaborate the factor(s) accompanying this observed survival advantage.

Clinical Impact of KIR2DS3 and KIR2DL3 Genes in Neuroblastoma Patients.

OBJECTIVE: Neuroblastoma is a common fatal tumor of childhood. Natural killer (NK) cells can exert direct cytotoxicity on tumor cells. The killer immunoglobulin-like receptor (KIR) family of NK cell receptors is involved in activation/inhibition of NK cells. In the KIR gene cluster, six of them (3DS1, 2DS1-5) encode receptors triggering activation, while seven of them (3DL1-3, 2DL1-3, 2DL5) encode receptors triggering inhibition. We aimed to assess the distribution of genetic polymorphisms of KIRs on the clinical course of neuroblastoma and provide guidance on potential therapeutic options. METHODS: Our study group included 50 neuroblastoma patients and 100 healthy children as controls. Twenty-eight patients were boys, and twenty-two were girls; median age was 36 months. Fourteen patients had stage 1, 2, 3, or 4S disease, and 36 patients had stage 4 disease. Isolated DNA from the peripheral blood was amplified for sequence-specific oligonucleotide probe analysis of 16 KIR genes. The Fisher's exact test was used to evaluate the variation of KIR gene distribution. RESULTS: All patients had a lower frequency of KIR2DS3 compared to the control group (p = 0.005). Evaluation of individual KIR genes/genotypes in patients with early stages (stage 1, 2, 3, and 4S) versus stage 4 disease revealed that the frequency of KIR2DS3 was increased in early stages (p = 0.023). Inhibitory KIR2DL3 was increased in the patient group compared to controls (p = 0.038). Furthermore, the frequency of KIR2DL3 was higher in stage 4 neuroblastoma patients compared to the patients with early stages (p = 0.023). CONCLUSION: Our data suggest a role for KIR2DS3 and KIR2DL3 in development of neuroblastoma. Thus, modulation of KIR2SD3 and/or KIR2DL3 expression or function might present a novel therapeutic strategy for neuroblastoma.

Comparison of Different Doses of Granulocyte Colony-stimulating Factor in the Treatment of High-risk Febrile Neutropenia in Children With Cancer.

Febrile neutropenia (FEN) is a significant side effect after chemotherapy, and it is known that using granulocyte colony-stimulating factor (G-CSF) has positive effects on treatment results. In this study, the effects of different G-CSF doses (5 to 10 mcg/kg/day) on treatment results in patients with high-risk FEN were evaluated. A total of 124 high-risk FEN episodes of 62 patients were enrolled in the study between June 2017 and October 2018. The episodes were divided into 2 groups according to G-CSF treatment doses, they received from 5 to 10 mcg/kg/day. The clinical characteristics of the patients, the treatments they received, laboratory findings, microbiologic results, and cost analysis were recorded. No statistically significant difference was found between 2 groups in terms of the mean duration of recovery from neutropenia, duration of fever, total length of hospital stay, duration of FEN episode, duration of G-CSF use, costs, bacteremia frequency, and other treatments. In patients with solid tumors, the cost of filgrastim was significantly higher in the high-dose G-CSF group. Using different doses of G-CSF in high-risk FEN episodes did not show any different effects on clinical and treatment results. The dose of 5 mcg/kg/day would be more appropriate in FEN treatment.

Thalassemia Major and Priapism: A Case Report of an Adolescent.

Priapism is defined as a prolonged pathologic penile erection without sexual stimulation. In children, priapism secondary to sickle cell disease or hematological malignancy is a frequent condition. Appropriate treatment of priapism varies; the treatment is primarily etiological, conservative management. In the present report, we aimed to present a case of asplenic thalassemia major who developed priapism, improved with hydration and ibuprofen treatment. Clinicians should take into account that priapism can be encountered in patients with thalassemia major. To our knowledge this is the second publication reporting the association between thalassemia major and priapism in childhood.

Outcome of autologous hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory Hodgkin's lymphoma.

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.

Treatment of Wilms tumor using carboplatin compared to therapy without carboplatin.

BACKGROUND: Wilms tumor (WT) is the most common pediatric malignant primary renal tumor. One of the main drugs used in treatment is actinomycin-D. This was not readily available in Turkey at one time. Carboplatin was used in the primary treatment of WT in order to prevent delays in treatment. The aim of this study is to present the results of patients with WT receiving carboplatin or actinomycin-D therapy. PROCEDURE: Forty-eight consecutive patients with WT treated between July 2005 and December 2011 were included in this retrospective study. The patients were treated according to Turkish Pediatric Oncology Group guidelines. Nineteen patients were treated with actinomycin-D and 29 with carboplatin (500 mg/m(2) /dose). The two groups were then compared in terms of 2- and 4-year overall survival (OS), event-free survival (EFS) and disease-free survival (DFS). RESULTS: Two- and four-year OS rates in the carboplatin group were 90.0% and 90.0%, compared to 100.0% and 88.0%, respectively, in the non-carboplatin group. Two- and four-year EFS levels in the carboplatin group were 92.0% and 88.0%, respectively, compared to 82.0% and 76.0% in the non-carboplatin group. Two-and four-year DFS levels in the carboplatin group were 92.0% and 86.0%, respectively, compared to 77.0% and 77.0% in the non-carboplatin group. CONCLUSIONS: The findings show that the carboplatin can be used as an alternative drug in the primary treatment of WT in the event that actinomycin-D is unavailable or not tolerated.

Dermatopathic lymphadenitis associated with human papilloma virus infection and verruca vulgaris.

Here we present a pediatric case of human papilloma virus associated with dermatopathic lymphadenitis (DL). A 5-year-old boy presented to the pediatric oncology clinic with swelling of the neck and warts on his lower jaw. His blood chemistry and complete blood count were normal, as was chest x-ray. HIV, EBV, CMV, and parvovirus serologies were negative. The patient was investigated for malignancy and lymphoma but no association was found. Histopathologic examination of the lymph node and the lesion revealed DL and verruca vulgaris, respectively. DL represents a benign form of reactive lymph node hyperplasia and described in patients with HIV and EBV infections. It is a rare entity described in patients with human papilloma virus infection. To our knowledge, this is the first report of DL in a patient with human papilloma virus infection.

The protective effect of hesperidin on methotrexate-induced intestinal epithelial damage in rats: an experimental study.

OBJECTIVE: The purpose of this experimental study was to evaluate the efficacy of hesperidin (HES) in protecting against methotrexate (MTX)-induced intestinal damage using histopathological and immunohistochemical techniques. MATERIALS AND METHODS: Seventy-eight male Wistar albino rats were divided into 4 groups that received (a) saline only (control group), n = 19; (b) HES only, n = 19; (c) MTX only, n = 19, and (d) MTX plus HES, n = 21. On the first day of the study, a single dose of MTX (20 mg/kg) was administered intraperitoneally to group 3 and 4 rats. The HES (200 mg/kg) was administered by gavage for 5 days. For the MTX plus HES group, HES (200 mg/kg) was administered by gavage for 5 days after MTX treatment. Rats were sacrificed on the 2nd, 4th and 6th day of the study. Tissue samples from the jejunum were taken for histopathological and immunohistochemical analysis. RESULTS: On the 4th day, crypt injury in the MTX plus HES group (1.00 ± 0.00) was less than that in the MTX group (2.00 ± 0.89; p < 0.05). The small intestinal damage score was lower in the MTX plus HES group (6.33 ± 0.82) as compared to the MTX group (8.00 ± 2.37). Inducible nitric oxide synthase and interleukin-8 levels were lower in the MTX plus HES group (65 and 25%, respectively) as compared to the corresponding values of the MTX group (80 and 52.5%, respectively). On the 6th day, the Ki-67 proliferation index in the MTX group (45%) was lower than that in the MTX plus HES group (76.67%) and the control group (p < 0.05). The small intestinal damage score was high in the HES group on the 4th day due to increased cellular infiltration. On the 6th day, the Ki-67 proliferation index rose in parallel with the decrease in cellular infiltration and therefore histopathological scoring. The proliferation-enhancing effect of HES also appeared in healthy rats. CONCLUSION: HES seemed to have a protective effect against MTX-induced intestinal injury.

Impaired growth, hematopoietic colony formation, and ribosome maturation in human cells depleted of Shwachman-Diamond syndrome protein SBDS.

BACKGROUND: Shwachman-Diamond syndrome (SDS), associated with SBDS mutations, is characterized by pancreatic exocrine dysfunction and marrow failure. Sdo1, the yeast ortholog of SBDS, is implicated in maturation of the 60S ribosomal subunit, with delayed export of 60S-like particles from the nucleoplasm when depleted. Sdo1 is needed for release of the anti-subunit association factor Tif6 from 60S subunits, and Tif6 may not be recycled to the nucleus when Sdo1 is absent. METHODS: To clarify the role of SBDS in human ribosome function, TF-1 erythroleukemia and A549 lung carcinoma cells were transfected with vectors expressing RNAi against SBDS. RESULTS: Growth and hematopoietic colony forming potential of TF-1 knockdown cells were markedly hindered when compared to controls. To analyze the effect of SBDS on 60S subunit maturation in A549 cells, subunit localization was assessed by transfection with a vector expressing a fusion between human RPL29 and GFP: we found a higher percentage of SBDS-depleted cells with nuclear localization of 60S subunits. Polysome analysis of TF-1 knockdown cells showed a decrease in free 60S and 80S subunits. We also analyzed the levels of eIF6 (human ortholog of Tif6) following near-complete knockdown of SBDS in TF-1 cells and found an approximately 20% increase in the amount of eIF6 associated with the 60S subunit. CONCLUSIONS: We conclude that knockdown of SBDS leads to growth inhibition and defects in ribosome maturation, suggesting a role for wild-type SBDS in nuclear export of pre-60S subunits. Furthermore, knockdown of SBDS may interfere with eIF6 recycling.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

The effect of nutrition and exercise training on irisin and semaphorin-3E levels in obese patients.

We aimed to firstly examine the effects of nutrition and exercise training on irisin, Sema-3E, biochemical and inflammatory parameters in obese patients. This study was conducted using 37 individuals were divided into three groups according to body mass index (BMI) as non-obese, 1nd degree and 2nd degree obese individuals. Nutrition and exercise training were applied to groups for eight weeks. Insulin resistance decreased in non-obese and 1st degree obese subjects. HsCRP values decreased only in the second degree obese individuals. Adiponectin values were significantly decreased in all three groups. There was a negative correlation between serum adiponectin and plasma irisin levels both before and after treatment. Sema-3E levels increased significantly in only the first degree obese individuals, whereas plexin-D1 values did not change significantly in any group. Our findings indicate that nutrition and exercise training we apply improved both anthropometric measurements and biochemical parameters in obese and non-obese individuals.

Efficacy of replacing actinomycin-D with carboplatin in Ewing sarcoma consolidation treatment: Single-center experience.

Background: Treatment of Ewing sarcoma (ES) requires multidisciplinary approach and deficiencies in treatment adversely affect the results. This study included patients diagnosed with ES and aimed to determine the factors affecting prognosis and investigate the efficacy of replacing actinomycin-D with carboplatin in consolidation treatment. Methods: Eighty-two pediatric ES patients diagnosed at a single institution between 2005 and 2020 were retrospectively evaluated. Clinical and epidemiological features, treatment modalities, prognostic criteria, and overall survival (OS) rates of patients revieved. In consolidation treatment, 22 patients were treated with actinomycin-D and 32 patients with carboplatin (500 mg/m2/dose), 24 patients could not receive consolidation treatment. The 5- and 10-year OS rates of the patients were compared. Results: The 5- and 10-year OS rates of the 82 patients with ES were 46% and 40%, respectively. The 5-year OS rates in the group with localized disease (n = 55) and metastasis (n = 27) at diagnosis were 54% and 26%, respectively (p = 0.006). When evaluated according to the consolidation treatment administered both the 5- and 10-year OS rates of the patients receiving actinomycin-D were 50%. The 5-year OS rate was 58% in the carboplatin group, and the 5- and 10-year OS rates of patients that did not receive consolidation treatment was 20%. Conclusions: Survival was significantly worse in the group that did not receive consolidation treatment. Furthermore, our results suggested that carboplatin could be used effectively as an alternative to actinomycin-D in ES consolidation treatment.

Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.