More than two courses of pre-transplant consolidation therapy benefits patients with acute myeloid leukemia in the first complete remission who underwent human leukocyte antigen-matched sibling allografts: a multicenter study / 中华医学杂志(英文版)

BACKGROUND@#Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.@*METHODS@#We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China.@*RESULTS@#With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P  = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P  = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P  = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P  = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P  = 0.013) than those with ≤ 2 courses.@*CONCLUSION@#Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.

Prognostic Factors and Predictive Value of MRD before Consolidation Therapy in Middle-risk Newly Diagnosed Young and Middle-aged Patients with AML / 中国实验血液学杂志

OBJECTIVE@#To explore the prognostic factors of young and middle-aged patients with acute myeloid leukemia (AML) and the predictive value of minimal residual disease (MRD) before consolidation therapy.@*METHODS@#The clinical data of 262 middle-risk young and middle-aged patients with AML treated in our hospital from January 2010 to December 2018 were selected retrospectively. All the patients were reached morphological leukemia-free state (MLFS) after induction chemotherapy, the overall and subgroup clinical data of the selected patients were analyzed. Cox regression model was used to evaluate the independent prognostic factors of middle-risk newly diagnosed young and middle-aged patients.@*RESULTS@#Among the patients less than 40 years old treated by consolidation therapy with PR-CT and allo-HSCT regimens, the 5-year cumulative leukemia-free survival(LFS) rates were 40.92% and 63.51%（P=0.01）respectively, while those over 40 years old were 23.61% and 49.14%（P=0.00）, respectively. The 5-year cumulative LFS rates of the patients treated by chemotherapy and achieved early remission and late remission were 63.51% and 41.33% （P=0.01）, respectively. The 5-year cumulative overall survival(OS) rates of the patients treated by PR-CT and allo-HSCT regimens were 23.65% and 69.32% (P=0.00), respectively, and the 5-year cumulative LFS rates were 26.44% and 52.30% (P=0.01). Among the patients treated by PR-CT consolidation treatment, the MRD-negative and MRD-positive cases were 74 and 60 cases, respectively. The 5-year cumulative incidence of relapse rate in the MRD-negative subgroup was significantly lower than those in the MRD-positive subgroup (P<0.05), the 5-year LFS rate and OS rate of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). For the patients treated by allo-HSCT consolidation treatment, the MRD-negative and MRD-positive cases were 66 and 62 cases, respectively. The 5-year cumulative incidence of relapse rate of the patients in MRD-negative subgroup was significantly lower than those in MRD-positive subgroup（P<0.05）, and the 5-year LFS and OS rates of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). The univariate analysis results showed that age, chromosome karyotype, MRD status after reaching MLFS, and consolidation treatment regime were all related to the prognosis of patients (P<0.05). The multivariate analysis results showed that age, MRD status after reaching MLFS, and consolidation therapy were the independent factors affecting the cumulative OS rate of the patients (P<0.05). Chromosome karyotype was an independent factor affecting the cumulative LFS rate of the patients (P<0.05). MRD status and consolidation treatment plan after reaching MLFS were the independent factors affecting the cumulative recurrence rate of the patients (P<0.05).@*CONCLUSION@#The OS rate of middle-risk young and middle-aged patients with newly diagnosed AML is independently related to age, MRD status after MLFS and consolidation therapy, while chromosome karyotype is independently related to cumulative LFS, and allo-HSCT consolidation therapy is recommended for middle-risk young and middle-aged AML patients after induction chemotherapy for MLFS, especially for those less than 40 years old and MRD positive before consolidation therapy.

Efficacy of Micro-Transplantation Consolidation Therapy for Patients with Acute Myeloid Leukemia after Complete Remission / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML).@*METHODS@#The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up.@*RESULTS@#Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened.@*CONCLUSION@#The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.

The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy / 中华血液学杂志

Objective: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia (AML) who received high-dose chemotherapy or autologous transplantation (intensive consolidation therapy) in the first complete remission (CR(1)) state. Methods: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. Results: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25 (31.6%) , 6 (7.6%) , 7 (8.9%) and 1 (1.3%) patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19 (24.1%) and 5 (6.3%) cases, respectively, and mutations of FLT3-ITD were confirmed in 5 (6.3%) cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival (OS) was seen in these patients (P=0.03) . Patients with C-KIT exon17 mutation had significantly shorter OS (P=0.01) and disease free survival (DFS) (P=0.006) compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS (P=0.048) and DFS (P=0.071) . Conclusion: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.

Is Second Look Laparoscopy for Diagnosing Remaining Ovarian Cancer Appropriate Further Treatment? / 이화의대지

OBJECTIVES: The aim of our study is to compare the findings of investigative modalities and second look laparoscopy in ovarian cancer and establish the safety and accuracy of second look laparoscopy for detecting ovarian cancer. METHODS: We retrospectively reviewed 11 patients with ovarian cancer treated by a single surgeon from 2006 to 2013. These patients were diagnosed at the time of primary cytoreductive surgery and received six cycles of combination chemotherapy. Then, they underwent second look laparoscopy. They were followed up with tumor markers monthly and PET-CT and/or CT scans. RESULTS: All 11 patients had undergone primary surgery followed by six cycles of consolidation chemotherapy. Eight patients had positive pathologic findings on second look laparoscopy (72.7 %). The CA 125 level was higher in one patient (12.5%). In seven patients who had positive results on second look laparoscopy, the value was well below normal limits (87.5%). Three patients had recorded increases in fluorodeoxyglucose uptake (37.5%). The increase in standardized uptake values in specific regions in the scans corresponded to positive biopsies from those regions. Seven patients who had positive findings on second look laparoscopy were treated with consolidation chemotherapy. The 5-year survival rate was 66.67%, and the 5-year recurrence rate was 33.33%. CONCLUSION: There are limitations to the accuracy of current investigative techniques, and we must rely on clinical correlation with these modalities for each case of second look laparoscopy. It is feasible to safely perform second look laparoscopy to detect remnant ovarian cancer.

Organ Preservation Strategies After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while preserving quality of life. Driven by patient demand and interest in preserving quality of life, numerous organ preservation treatment strategies for managing rectal cancer are rapidly evolving. Herein, the flow of research in organ preservation strategies and counter arguments are discussed.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results

PURPOSE: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. MATERIALS AND METHODS: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. RESULTS: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. CONCLUSION: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

Isolated pulmonary Langerhans cell histiocytosis in a 10-month-old infant

Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation and accumulation of abnormal dendritic (Langerhans) cells in various organs. Pulmonary involvement, although rare in children, has been reported in 20%–50% of childhood cases of multisystem LCH. Isolated pulmonary LCH in children, especially in infants, is still rarer, but should be suspected in those with cystic lung disease. We report a case of a 10-month-old boy who presented with chronic dyspnea and whose chest computed tomography (CT) scan demonstrated cystic lesions. Lung biopsy established the diagnosis of LCH; microscopy revealed a background of lymphocytes and eosinophils with kidney-shaped abnormal cells. These abnormal cells were positive for S-100, CD207 (Langerin), and CD1a on immunohistochemical staining. Chemotherapy was administered using a cytotoxic agent (vinblastine) and a steroid. After 12 weeks of induction chemotherapy, although no significant change in cyst size was noted on chest CT, clinical symptoms improved. Consolidation chemotherapy was then administered for 1 year. Thereafter, chest CT findings demonstrated a significant decrease in cyst size and a significant increase in the volume of normal lung parenchyma. Therefore, aggressive treatment of isolated pulmonary LCH in infants with severe tissue destruction and symptoms seems warranted.

Impact of duration of antibiotic therapy on the prognosis of patients with acute myeloid leukemia who had Gram-negative bloodstream infection in consolidation chemotherapy / 中华血液学杂志

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10(9)/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion: Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

Comparison of the efficacy of decitabine combined with micro-transplantation or priming regimen as consolidation treatment for older patients with acute myeloid leukemia / 中华血液学杂志

Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period. Results: There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ(2)=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively). Conclusion: DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.

Lymphocyte Count before First Consolidation Therapy Is A Predictor of Relapse free Survival in Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse.</p><p><b>METHODS</b>The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10/L) and low lymphocyte count group (L-Lym<1.2×10/L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed.</p><p><b>RESULTS</b>Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01).</p><p><b>CONCLUSION</b>The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.</p>

Costo efectividad de las pruebas para estratificar riesgo en el tratamiento de la leucemia mieloide aguda (LMA) en población pediátrica / Cost-effectiveness of risk stratification tests for the treatment of acute myeloid leukemia in pediatric patients

RESUMEN Objetivo Estimar la razón de costo-efectividad de las pruebas para estratificación del riesgo en pacientes pediátricos con Leucemia Mieloide Aguda (LMA). Métodos Se construyó un árbol de decisión con años de vida ganados como medida de efectividad. Los costos fueron estimados desde la perspectiva del sistema de salud colombiano. En los costos de la estratificación se incluyeron los costos del tratamiento consecuente con ella. Los precios de medicamentos fueron tomados del SISMED 2008 y el valor monetario de los procedimientos se extrajo del manual tarifario del ISS 2001 adicionando el 30 %. Todos los costos se expresaron en pesos colombianos del 2010 y el producto interno per-cápita de ese año fue empleado como umbral de costo efectividad. Se condujeron análisis de sensibilidad univariados y probabilísticos. Resultados La razón de costo-efectividad incremental de las pruebas de estratificación a todos los pacientes, fue de $8 559 944. Los resultados son sensibles a las probabilidades de recaída, supervivencia al trasplante y efectos secundarios. Conclusión Las pruebas para estratificación del riesgo en LMA son costo-efectivas dentro del sistema de salud colombiano.(AU)

ABSTRACT Objective To estimate the cost-effectiveness of risk-stratification tests for the treatment of acute myeloid leukemia (AML) in pediatric patients. Methods A decision-tree model was built using Life Years Gained as a measure of effectiveness. Costs were estimated considering the perspective of the Colombian health system. Stratification costs included treatment costs based on said stratification. Drug prices were taken from SISMED (Drug Price Information System) 2008 and the monetary value of the procedures was extracted from the ISS 2001 rate manual, plus 30%. All costs were expressed in Colombian pesos for 2010 and the gross domestic product per capita of the same year was used as a cost-effective threshold. Univariate and probabilistic sensitivity analyzes were performed. Results Risk stratification tests have an incremental cost-effectiveness ratio of COP 8,559,944. These results are sensitive to changes in probabilities of relapse, transplant survival and side effects. Conclusion Risk stratification tests for AML treatment in pediatric patients are cost-effective in the context of the Colombian health care system.(AU)

The outcomes of intensified 5-fluorouracil plus leucovorin chemotherapy for preoperative chemoradiation in rectal cancers

PURPOSE: The clinical benefit of intensified neoadjuvant chemoradiotherapy (CRT) in rectal cancer has not been proved. We investigated clinical outcomes of intensified 5-fluorouracil plus leucovorin (5-FU/LV) chemotherapy.METHODS: We retrospectively analyzed 45 patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant CRT between 2010 and 2015. Intensified group took additional 1 cycle of 5-FU/LV chemotherapy after radiation completion (resting period) before surgery, compared to conventional group.RESULTS: Eighteen patients were in conventional group and 27 were in intensified group. Median follow-up duration was 33.7 months (range, 7.8–75.6 months). Complete response rate was 11.4% (5/45). Twelve patients in conventional group and 16 patients in intensified group achieved downstaging (P=0.435). In aspect of toxicity, anemia and thrombocytopenia tended to be more frequent in intensified group without statistical difference. There was also no difference in survival between two groups.CONCLUSION: The intensified CRT with additional 1 cycle of 5-FU/LV in rectal cancer revealed no clinical benefit compared to conventional regimen. Considering that the adverse event was minimal and generally acceptable, further research with additional cycles of 5-FU/LV is needed to prove a real benefit of intensified CRT.

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients / 부인종양

OBJECTIVE: To evaluate the efficacy and toxicity of paclitaxel plus carboplatin (TC)-based concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB/IVA cervical cancer patients. METHODS: We reviewed the medical records of FIGO stage IIIB/IVA cervical cancer patients (n=30) who had been intended to be treated with TC-based CCRT followed by consolidation chemotherapy (TC-CCRT-group) from April 2012–May 2016. Patients who had been treated with CCRT involving a single platinum agent (CCRT-group; n=52) or definitive radiotherapy alone (RT-group; n=74) from January 1997–September 2012 were also identified and used as historical controls. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of the 30 patients included in the TC-CCRT-group, 22 patients (73.3%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up of 35 months, 9 patients (30.0%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 67.9% and 90.8%, respectively. In comparisons with historical control groups, the survival outcomes of TC-CCRT-group was significantly superior to CCRT-group in terms of OS (p=0.011) and significantly superior to RT-group in terms of both PFS (p=0.009) and OS (p<0.001). CONCLUSION: TC-based CCRT followed by consolidation chemotherapy is safe and effective. A randomized controlled study needs to be conducted to further evaluate the efficacy of this multimodal approach in this patient population.

Concurrent chemoradiotherapy followed by docetaxel and cisplatin consolidation chemotherapy in elderly patients with esophageal carcinoma / 中南大学学报(医学版)

To investigate the clinical efficacy of consolidation chemotherapy with docetaxel and cisplatin (DP) in elderly patients of esophageal cancer.
 Methods: Seventy-nine elderly patients of esophageal cancer were randomly divided into the treatment group (38 patients) and the control group (41 patients). Intensity modulated radiation therapy (IMRT) was applied in both groups and prescribed dose was set to 56 to 59.4 Gy in 28 to 33 fractions. The concurrent chemotherapy regime for both groups was as follow: docetaxel 25 mg/m2 plus cisplatin 25 mg/m2, per week. After concurrent chemoradiotherapy, consolidated chemotherapy was applied to the treatment group with docetaxel 60 mg/m2 and cisplatin 75 mg/m2 
for 3 weeks in one cycle. There was no subsequent treatment for the control group.
 Results: The clinical efficacy was assessed in 76 patients. For the treatment group, 31 patients (response rate, 89.2%) obtained effective response, including 10 cases with complete response (CR) and 21 cases with partial response (PR), both of which were significantly more than that in the control group (response rate, 61.5%), with 9 cases of CR and 15 cases of PR. The median progression-free survival was 19.7 months in the treatment group, clearly longer than that in the control group (10.8 months, P=0.04). The overall survival for 1-year, 2-year and 3-year were 78.5%, 57.9% and 37.8% in the treatment group versus 61.2%, 42.3% and 22.7% in the control group (P>0.05), respectively. Grade 1 and 2 adverse effects were commonly observed in both groups, such as hematologic toxicity and radiation-induced esophagitis, but there was no significant difference between the two groups. 
 Conclusion: For elderly patients with esophageal carcinoma, the overall response rate can be significantly improved by concurrent chemoradiotherapy with subsequently consolidated chemotherapy based on docetaxel and cisplatin..

Costo-efectividad de los tratamientos de consolidación para la leucemia mieloide aguda en niños en riesgo alto en el sistema de salud colombiano / Cost-effectiveness of consolidation treatments for acute myeloid leukemia in high-risk pediatric patients within the Colombian healthcare system

Introducción. La leucemia mieloide aguda representa alrededor del 20 % de las leucemias en menores de 18 años. Actualmente, solo existen dos alternativas de tratamiento de consolidación: la quimioterapia y el trasplante con progenitores hematopoyéticos. Objeti vo. Evaluar el costo-efectividad del trasplante alogénico con progenitores hematopoyéticos de donantes emparentados o no emparentados, en comparación con la quimioterapia de consolidación en niños de alto riesgo con leucemia mieloide aguda. Materiales y métodos. Se construyó un árbol de decisiones utilizando los años de vida ganados como resultado. Los costos y probabilidades se extrajeron de estudios y reportes que se encuentran en la literatura científica. El umbral de costo-efectividad fue tres veces el producto interno bruto per cápita de 2010. Se hicieron análisis de sensibilidad univariados y probabilísticos, así como una curva de aceptabilidad. Resultados. Al comparar el trasplante de donante emparentado o no emparentado con los ciclos de quimioterapia, se obtuvieron tasas de costo-efectividad incremental de COP$ 9´226.421 (USD$ 4.820) y COP$ 6´544.116 (USD$ 3.419), respectivamente, cifras estas inferiores al producto interno bruto per cápita: COP$ 12´047.418 (USD$ 6.294). El trasplante resultó ser costo-efectivo en 70 % de las simulaciones y con mayor probabilidad de serlo cuando había disposición a pagar cantidades superiores a COP$ 7´200.000 (USD$ 3.762). Conclusión. El trasplante alogénico (emparentado o no) en Colombia resultó ser costo-efectivo frente al tratamiento de consolidación en niños de alto riesgo con leucemia mieloide aguda.

Introduction: Acute myeloid leukemia represents about 20% of leukemias in minors under 18 years old. At present, there are only two consolidation treatment alternatives: Chemotherapy and stem-cell transplantation. Objective: To evaluate the cost-effectiveness of unrelated and related hematopoietic stem cell transplantations, versus chemotherapy consolidation in pediatric patients with high-risk acute myeloid leukemia. Materials and methods: A decision tree was constructed with life-years gained as the outcome. Costs and probabilities were extracted from the literature. Probabilistic sensitivity analyses and acceptability curves were computed. The cost-effectiveness threshold was three times the 2010 per capita gross domestic product. Results: When compared to consolidation chemotherapy cycles, related and unrelated hematopoietic stem-cell transplantation had incremental cost-effectiveness ratios of COP$ 9,226,421 (USD$ 4,820) and COP$ 6,544,116 (USD$ 3,419) respectively, which are lower than the per capita gross domestic product (COP$ 12,047,418, USD$ 6,294). Transplant proved to be cost-effective in 70% of the simulations and had a higher probability of the willingness to pay being over than COP$ 7,200,000 (USD$ 3,762). Conclusion: In Colombia, related and unrelated hematopoietic stem-cell transplants are cost-effective alternatives to consolidation treatment for high-risk acute myeloid leukemia in pediatric patients.

Inadvertent Transmission of a Donor's Constitutional Chromosome Abnormality after Hematopoietic Stem Cell Transplantation

A pre-transplant screening work-up of donors for allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Inadvertent transmission of malignancy from donors with subclinical diseases to recipients has been reported recently in several cases. A 49-year-old male was diagnosed with acute myeloid leukemia. He underwent a course of induction chemotherapy and achieved cytogenetic complete remission (CR). He was treated with an additional cycle of consolidation chemotherapy followed by full matched sibling allogeneic HSCT due to an additional deletion in 9q known as an adverse prognostic factor. Post transplantation bone marrow biopsy revealed molecular CR, but conventional cytogenetics identified the presence of 46,XY,t(1:2)(p32:q35). A cytogenetic analysis of the donor graft specimen revealed t(1:2). We confirmed the donor origin of t(1:2). We report the first case of a person with constitutional t(1;2) serving as a stem cell donor.

Bullae-Forming Pulmonary Metastasis from Choriocarcinoma Presenting as Pneumothorax

Gestational trophoblastic disease (GTD) is a condition of uncertain etiology, choriocarcioma, or placental-site hydatidiform moles, invasive moles, choriocarcinoma, and placental-site trophoblastic tumors. It arises from the abnormal proliferation of trophoblastic tissue and spreads beyond the uterus hematogenously. The early diagnosis of GTD is important to ensure timely and successful management and the preservation of fertility. We report the unusual case of a metastatic choriocarcinoma that formed bullae on the lung surface and presented as recurrent pneumothorax in a 38-year-old woman with elevated beta-human chorionic gonadotropin (hCG) levels. She underwent thoracoscopic wedge resection of the involved lung and four subsequent cycles of consolidation chemotherapy. No other evidence of metastatic disease or recurrent pneumothorax was noted during 22 months of follow-up. GTD should be considered in the differential diagnosis of spontaneous pneumothorax in reproductive-age women with an antecedent pregnancy and abnormal beta-hCG levels.