Clinical Study on Dynamic Detection of Minimal Residual Disease in Acute Myeloid Leukemia by Multiparameter Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry.@*METHODS@#MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis.@*RESULTS@#ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015).@*CONCLUSION@#The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.

Application of near infrared fluorescence imaging in detection of residual cancer in oral squamous cell carcinoma / 中华肿瘤杂志

Objective: Local recurrence is the main cause of treatment failure in patients with oral squamous cell carcinoma (OSCC). This study was proposed to investigate the feasibility of near infrared fluorescence (NIF) via indocyanine green (ICG) for monitoring surgical marginal in operation for OSCC patients. Methods: In 35 patients with OSCC treated surgically in the Department of Oral and Maxillofacial Surgery, Nanjing University School of Medicine, from January 2019 to June 2020, ICG (0.75 mg/kg) was administered intravenously via elbow vein at (12±1) hours before surgery, and NIF was performed intraoperatively on the surgical field and the cut edge of the surgically excised specimen, and fluorescence intensity was measured for OSCC tissue and normal oral mucosa, abnormal fluorescence signals were taken and subjected to rapid cryopathological examination. Correlation between NIF tumor boundary grading and pathological tumor boundary grading was analyzed by Spearman correlation analysis. Results: Clear ICG NIF was obtained for tumor lesions in all 35 patients, with a positive rate of 100%. The fluorescence intensity of OSCC tissue was (412.73±146.56) au, which was higher than that of normal oral mucosa tissue [(279.38±82.56) au, P<0.01]. Abnormal fluorescence signals were detected at the tumor bed and the cut edge of the surgical resection specimen in 4 patients, of which 2 cases were pathologically confirmed as cancer cell residue and 2 cases as inflammatory cell infiltration. The rate of positive detection of cut margins using ICG NIF technique in OSCC was 5.7% (2/35). Twenty of the 35 OSCC patients had grade 1, 11 of grade 2, and 4 of grade 3 tumor borders revealed by NIF of surgical resection specimens, which was positively correlated with pathological tumor border (r=0.809, P<0.001). Conclusions: ICG NIF technique can effectively detect the residual cancer cells at the incision margin, which is of great clinical value in reducing local recurrence of OSCC after surgery due to intraoperative cancer residue.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen.@*METHODS@#106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children.@*RESULTS@#The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon.@*CONCLUSION@#Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

Establishment of An Animal Model of Acute B Lymphoblastic Leukemia with Minimal Residual Disease / 中国实验血液学杂志

OBJECTIVE@#To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease.@*METHODS@#The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis.@*RESULTS@#There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections.@*CONCLUSION@#The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.

Detection of Minimal Residual Disease in Acute Myeloid Leukemia by Multi-color Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To establish 10-color fluorescent antibody combination panels for the detection of minimal residual disease (MRD) of acute myeloid leukemia (AML) in our laboratory and discuss the value of clinical application.@*METHODS@#According to the antigen expression characteristics of leukemia cells of incipient AML patients, MRD in bone marrow were detected by multiparameter flow cytometry, and the test results were compared with both bone marrow cell morphology and PCR results, then 10-color fluorescent antibody combination panels in our lab for MRD detection was determined.@*RESULTS@#The immunophenotypic characteristics of 392 incipient patients with AML in the First Affiliated Hospital of Zhengzhou University were analyzed, among them 357 (91.07%) cases showed abnormal immunophenotypes, which mainly included cross-lineage expression, cross-stage expression, deficiency of antigen expression or abnormal antigen intensity and other abnormal expression. The 10-color fluorescent antibody combination panels established according to abnormal immunophenotypic characteristics of leukemia cells were applied for detecting MRD in 156 patients with AML, the positive rate (43.6%) was higher than 26.8% of morphology, and the results were highly consistent with PCR detection results (96.49%), moreover, the recurrence rate of MRD positive patients (86.96%) was significantly higher than 5.75% of MRD negative patients. Therefore, this method could truly reflect the load of leukemia cells and prompt change of disease condition.@*CONCLUSION@#Multiparameter flow cytometry can detect various abnormal immunophenotypes of AML. The 10-color fluorescent antibody combination panels in our lab based on the characteristics of antigens expression in leukemia cells can well detect MRD of leukemia cells, so as to predict relapse and provide basis for clinical treatment.

The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients.@*METHODS@#B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients.@*RESULTS@#There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients.@*CONCLUSION@#Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).@*METHODS@#A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.@*RESULTS@#Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05).@*CONCLUSIONS@#Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.

The effect of CAM comprehensive nursing interventions on the improvement of quality of life to patients with breast cancer and gynaecological tumours

Breastcancerin females, which is consideredthe most dreadfuldisease in India andthe worldas compared toother gynaecological cancers,demands extensive care and proper medicationin order to control itsprogressive growth. In addition to the conventional care ofthe patients, Complementary andAlternative Medicine(CAM)is administeredin a controlled way through proper guidance and counselling in orderto attainimprovedphysical andmental health forthe patients.Objective: The aim of the study wasto assess the effectiveness of CAMcomprehensive nursing interventionsand their benefit forpatients who havebreast cancer and gynaecological tumours.Methods: Statistical data was used to map the adult womendiagnosed with breast and gynaecological cancer and who were set to start new chemotherapy treatments. A total of 450 patients from different states of East India were enrolled in the studyover a period of four years. The patients wereselectedbased on their preference for undergoing CAM.The research was conducted usingacross-sectionalanonymous self-administered questionnaireto examine women's perspectivestowards the use of CAM and itseffect on their mental andphysical health.Results:42%of the women preferred theuseofCAM astheir alternative treatment. Breast cancer patients disclosed that 48.1% of them had used CAM and 39% of women with gynaecological cancersstated that they had usedCAM. The results further indicated a less frequent deteriorationin the health of CAM users(38.4%) thantonon-users(55%). In terms of those who utilizedvitamins and nutritional diets,60% of the participants reported using a proper diet, including antioxidants, minerals, vitamins and herbs etc. 37% opted for spiritual healing through yoga, 26% utilized energy healing, 42.4% utilized acupuncture,72% preferred massagesand 23% of patients utilized chiropractic methods.The use of CAM was foundmainlyin the patients with proper education and awareness and those with a family history of cancer who were not receiving the necessary care from their previous primary physician.Conclusion:CAM still requiresextensive research in terms of its applications in dealing with patients and in orderto successfully launch programmes aimed at promoting its useworldwide andto eradicate all the other false notions about it.[Ethiop. J. Health Dev. 2022; 36(2):000-000]Keywords: Breast Cancerand gynaecological tumours,Complementary And Alternative Medicine (CAM), Complementary Oncology,Quality Of Life, Nutritional Diet and Spiritual Healing, HRQL (Health-Related Quality Of Life).IntroductionCancer has been the primaryconcern in Indiafrom the onset,resulting in thousands of deaths due to the lack of adequatemedication and therapy.Breast cancer is considered to bea common invasive form of cancer which is responsible for the second highest mortality rate among the primaryfatal conditions of cancer-causing deaths in women. Under the National Cancer Registry Program,the breast, cervix, uteri,and oral cavity(7)are the most common cancer sitesin women. According to statistics, 50-60% of all cancers amongIndian women are commonly found inthe cervix uteri, breast, corpus uteri and ovaries,which are the main organs forcancer invasion. The percentage of women who experience these types of cancer is increases, with more women becoming susceptible to breast cancer, in women up to 3-8% suffer fromovarian cancer,0.5-4.8%have cancer of the corpus uteri, 1-3% have vulva and/or gestational trophoblastic tumours and a staggering75,000 or more women have breast cancer. With the advancements of the disease through time,research programs were also improved in order to enable the improvement of existing measures and/or the development of new measures aimed at combating the diseas and decreasing mortality rates. Apart from the conventional chemotherapy technique,various other programs have been introduced andencorporated into treatment regimes in order to improve the lives of those who are affected by cancer.Complementary andAlternative Medicine (CAM) emphasizesthe methods and practices that are therapeutic and which help diagnose or curethe disease,these methods are intended tocomplement the conventional methods and can be used in place of mainstream medicine. Women with breast cancer and other gynaecological tumoursare increasingly inclined towards the use of CAM. With the increasing number of cancer reports in Indiaand the world,and with the principal amount leading to mortality, women with proper education and awareness are inclined to choosealternative methods rather than the old conventional ones. The side-effects resulting from the chemotherapy are immense and toxic,which is one of the reasons women are inclined to choose.Various research projects and cumulative studies have been conducted in order to review and discoverthe

Histopathological pattern of Orbito-Ocular Lesions, a retrospective hospital-based study spanning 15 years

Background: Many previous studies on orbito-ocular lesions are skewed in favour of the neoplastic lesions in general and the malignant lesions in particular. This, therefore, creates a vacuum on the spectrum of these lesions, thus may result in problematic diagnostic bias by the ophthalmologist and pathologist. Objective: To give the spectrum and relative frequencies of orbito-ocular biopsies and by extension orbito-ocular lesions/diseases at the University of Benin Teaching Hospital (UBTH). Materials and Methods: A retrospective descriptive study of all cases of orbito-ocular biopsies with histopathologic diagnosis. Results: There were 236 orbito-ocular biopsies. The male to female ratio was slightly in favour of the females. Orbito-ocular biopsies had a wide age range that spanned from the 1st to 10th decade, mean age in the 3rd decade (20-29years) and a peak age in the 1st decade (0-9 years). The neoplastic lesions were the prevalent indication for orbito-ocular biopsies (63.72%) while the conjunctiva (58.10%) was the most common site for orbito-ocular biopsies. Conclusion: This study noted a wide array of orbito-ocular lesions for which biopsies were done for histopathological diagnosis. This we hope will in no small measure increase the diagnostic precision of the ophthalmologist and the pathologists in our own environment

A spectrum of findings on computed tomography in paediatric abdominal and pelvic tumours in a Ghanaian teaching hospital

Objectives: To review the Computed Tomography( CT )features of pediatric oncological patients with abdominal and pelvic tumours and correlate these findings with their histopathological diagnosis Design: This was a retrospective cross-sectional facility-based study. Setting: This study was conducted in the Pediatric Oncology Unit and Radiology Department of the Korle Bu Teaching Hospital Participants: Fifty-six pediatric oncology patients with contrast-enhanced abdominal and pelvic CT scans. Data Collection: The abdominal and pelvic CT scans findings, patient biodata, and histopathology reports of oncology patients over four years were reviewed Statistical analysis: Simple descriptive statistics using frequency distribution, percentages, means, and standard deviation were used to describe the various variables and presented tables. Results: The four commonest tumours were nephroblastoma, neuroblastoma, lymphoma, and hepatoblastoma. The mean age at diagnosis was 4.8 years, with a slightly higher male predominance. The majority of the tumours were extremely large at presentation. Overall, the CT ­ histopathology concordance was 79.2%. Conclusion: Abdominal and pelvic CT scans play an important role in the diagnostic workup of pediatric malignancies by ensuring early and accurate diagnosis of these tumour

Immunohistochemical Study and Clinicopathologic Correlation of Cox-2 and Her-2 Expression in Colorectal Carcinoma: A 5-Year Retrospective Study

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects. OBJECTIVES: To evaluate the expression of COX-2 and HER2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer. METHODS: Fifty-three paraffin-embedded tissue blocks of colorectal resections and corresponding patient information were retrieved from the archives of the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital.A 4-micron slide section was obtained from each specimen and immunohistochemistry for COX-2 and HER-2 expression was performed. RESULTS: Mean age of cases was 53.9years with an almost equal M:F ratio of 1.12:1. Half of the cases were moderately differentiated adenocarcinoma and 17% were high grade tumors.Eighty three percent of the tumours showed positive cytoplasmic COX-2 expression and extremely low membranous HER-2 positivity was observed in 2%. There was no significant correlation between COX-2 expression and age, gender, tumour location, tumour size, depth of invasion or lymph node status.However, COX-2 expression revealed a significant correlation with tumour grade (p= 0.013). CONCLUSION: This study detects a high COX-2 and low HER2 expression in colorectal cancer using immunohistochemistry,suggesting a possible role for COX-2 in CRC pathogenesis.This report should trigger further investigations of both markers vis-à-vis the management of CRC in our environment. WAJM 2022; 39(11): 1134­1140.

Quimioterapia intensiva asociada a imatinib en leucemia linfoblástica aguda del adulto, Philadelphia positivo. Experiencia en un hospital público / Intensive chemotherapy with tyrosine kinase inhibitors in philadelphia-positive acute lymphoblastic leukemia

Background: Before the advent of tyrosine kinase inhibitors (TKIs), patients with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ALL) had a poor prognosis. The association of TKIs to intensive chemotherapy (CT) improved outcome. Aim: To evaluate results of an intensive CT protocol including TKI in a public hospital in Santiago, Chile. Material and Methods: All patients with Ph+ALL diagnosed between January 2010 and February 2019, and who met inclusion criteria for intensive CT, received the Ph+ALL national protocol in association with imatinib and were included in this analysis. Results: Thirty-five patients aged 15 to 59 years received treatment. Complete response (CR) was obtained in 97%. Measurable residual disease (MRD) was negative in 61% (19/31 evaluable cases) during follow-up, and 55% (16/29) were MRD (-) before three months. Relapse was observed in 13 cases. Three patients underwent allogeneic hematopoietic stem cell transplant (HSCT), two in CR1. The overall survival (OS) and event-free survival (EFS) at three years were 52 and 34%, respectively. In patients who achieved MRD negativity before three months, no statistically significant differences in OS (64 and 42% respectively, p = 0.15) or EFS (35 and 32% respectively, p = 0.37) were observed. Conclusions: The prognosis of Ph+ALL improved with the association of imatinib to intensive CT. MRD-negative status before three months in this series was not significantly associated with better outcomes. Our series suggests that the Ph+ALL national protocol associated to TKI is a therapeutic alternative with high CR and aceptable MRD (-) rates.

Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation

Abstract Introduction: The minimal residual disease (MRD) status plays a crucial role in the treatment of acute lymphoblastic leukemia (ALL) and is currently used in most therapeutic protocols to guide the appropriate therapeutic decision. Therefore, it is imperative that laboratories offer accurate and reliable results through well standardized technical processes by establishing rigorous operating procedures. Method: Our goal is to propose a monoclonal antibody (MoAb) panel for MRD detection in ALL and provide recommendations intended for flow cytometry laboratories that work on 4-color flow cytometry platforms. Results and conclusion: The document includes pre-analytical and analytical procedures, quality control assurance, technical procedures, as well as the information that needs to be included in the reports for clinicians.

Elastografía cualitativa por ultrasonido endoscópico en la reestadificación del tumor de recto irradiado / Qualitative elastography by endoscopic ultrasound in the restaging of the irradiated rectal tumor

Introducción: En la reestadificación del paciente con tumor de recto irradiado, la elastografía cualitativa por ultrasonido endoscópico puede identificar la fibrosis y diferenciarla del tumor residual. Objetivo: Determinar la utilidad de la elastografía cualitativa por ultrasonido endoscópico en la reestadificación del tumor de recto irradiado. Métodos: Estudio observacional y descriptivo (serie de casos), en 31 pacientes con tumor de recto irradiado, reestadificados mediante elastografía cualitativa por ultrasonido endoscópico. Para determinar la utilidad de la elastografía se calcularon: sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo, índice de Youden y concordancia diagnóstica según índice kappa, de la elastografía y del ultrasonido endoscópico por separado, estos resultados fueron comparados en ambas pruebas diagnósticas. El estudio histológico de la pieza quirúrgica fue el estándar de referencia. Resultados: El índice de concordancia del ultrasonido endoscópico (77,4 por ciento), por elastografía (87,1 por ciento). El ultrasonido endoscópico mostró mayor sensibilidad y valor predictivo negativo que la elastografía, por lo que la posibilidad de descartar presencia de tumor con un resultado negativo fue superior. La elastografía tuvo mayor especificidad (77,78 por ciento) y valor predictivo positivo (90,91 por ciento) que el ultrasonido endoscópico (22,22 y 75,86 por ciento); fue más útil para confirmar el diagnóstico de tumor. Conclusiones: La utilidad de la elastografía cualitativa asociada al ultrasonido endoscópico, en la reestadificación del tumor de recto irradiado, consiste en incrementar la especificidad del estudio y discernir mejor entre la fibrosis y el tumor residual(AU)

Introduction: Qualitative endoscopic ultrasound elastography can identify fibrosis and differentiate it from residual tumor in the re-staging of patients with irradiated rectal tumors. Objective: To determine the usefulness of qualitative endoscopic ultrasound elastography in the re-staging of the irradiated rectal tumor. Methods: An observational and descriptive study (series of cases) was carried out in 31 patients with irradiated rectal tumor, restaged by means of Qualitative elastography by endoscopic ultrasound. To determine the usefulness of elastography, the following were calculated: sensitivity, specificity, positive predictive value, negative predictive value, Youden index and diagnostic agreement according to kappa, elastography and endoscopic ultrasound separately; these results were compared in both diagnostic tests. The histological study of the surgical specimen was the reference standard. Results: The concordance index of endoscopic ultrasound (77.4 percent), that obtained by elastography (87.1 percent). Endoscopic ultrasound showed greater sensitivity and negative predictive value than elastography, so the possibility of ruling out the presence of a tumor with a negative result was higher. Elastography had greater specificity (77.78 percent) and positive predictive value (90.91 percent) than endoscopic ultrasound (22.22 and 75.86 percent); it was most helpful in confirming the tumor diagnosis. Conclusions: The usefulness of qualitative elastography associated with endoscopic ultrasound, in the re-staging of the irradiated rectal tumor, consists in increasing the specificity of the study, thus allowing a better discernment between fibrosis and residual tumor(AU)

Detección por citometría de flujo de la enfermedad mínima residual en las leucemias agudas / Detection of the minimal residual disease by flow cytometry in patients with acute leukemia

Introducción: La enfermedad mínima residual es la permanencia de células leucémicas residuales en niveles subclínicos luego de la remisión de la enfermedad. Esta condición incrementa el riesgo de recaída y mortalidad. Objetivo: Caracterizar factores clínicos y moleculares de pacientes con leucemias agudas y enfermedad mínima residual detectada por citometría de flujo en una institución de alta complejidad de la ciudad de Medellín, Colombia durante los años 2015 - 2017. Metodología: Este es un estudio descriptivo retrospectivo, que incluyó pacientes con leucemia diagnosticada por citometría de flujo. Se realizó un muestreo no probabilístico de casos consecutivos. La información recolectada fue digitada en una base de datos en Excel, y el análisis se realizó a través del programa IBM SPSS Versión 24, empleando según la naturaleza de cada variable frecuencias absolutas y relativas, promedio y desviación estándar o mediana y rangos intercuartílicos según su distribución. Resultados: Se incluyó un total de 60 pacientes con predominio del sexo masculino 63,3 por ciento (38). El diagnóstico más frecuente fue la leucemia linfoide 78,3 por ciento (47). Del total de pacientes incluidos, 36,6 por ciento (22) fue positivo para enfermedad mínima residual; 28,3 por ciento recibió trasplante de médula ósea y el 10 por ciento (6) presentó compromiso de líquido cefalorraquídeo. En la segunda citometría en pacientes con enfermedad mínima residual, 90,9 por ciento (20) expresaba CD45+. El 31,8 por ciento (7) de los pacientes con enfermedad mínima residual presentó recaída. Conclusión: La enfermedad mínima residual es una condición frecuente en pacientes con leucemias agudas que requiere seguimiento y constituye un factor pronóstico relevante(AU)

Introduction: The minimal residual disease is the permanence of residual leukemic cells at subclinical levels after remission of the disease. This condition increases the risk of relapse and mortality. Objective: To characterize the clinical and molecular factors of patients with acute leukemias and minimal residual disease detected by flow cytometry in a highly complex institution in the city of Medellín, Colombia during the years 2015 - 2017. Methodology: This is a retrospective descriptive observational study, which included patients with leukemia diagnosed by flow cytometry. A non-probabilistic sampling of consecutive cases was carried out. The information collected was entered into a database in Excel, and the analysis was carried out through the IBM SPSS Version 24 program, using absolute and relative frequencies, average and standard deviation or median and interquartile ranges, according to the nature of each variable and its distribution. Results: 60 patients were included in which male sex predominated with 63.3 percent (38). The most frequent diagnosis was lymphoid leukemia with 78.3 percent (47). Of the total patients included, 36.6 percent (22) were positive for minimal residual disease; 28.3 percent received a bone marrow transplant and 10 percent (6) had a cerebrospinal fluid compromise. In the second cytometry of the patients with minimal residual disease, 90.9 percent (20) expressed CD45 +. 31.8 percent (7) of the patients with minimal residual disease relapsed. Conclusion: Minimal residual disease is a frequent pathology in patients with acute leukemias that requires follow-up and constitutes a relevant prognostic factor(AU)

Enfermedad residual medible mediante reordenamientos de inmunoglobulinas y receptores de linfocitos-T / Measurable residual disease by rearrangements of immunoglobulins and T-lymphocyte receptors

Resumen Las leucemias agudas constituyen la neoplasia más frecuente en pacientes pediátricos. Actualmente, el 80% de los niños con leucemia linfoblástica aguda (LLA) logran curarse con quimioterapia con vencional pero el 20% de los mismos presentarán una reaparición de la enfermedad. La enfermedad residual medible (ERM) ha sido descripta como un importante factor pronóstico, que permite evaluar la respuesta de los pacientes al tratamiento. Una de las técnicas más sensibles par a estudiar ERM es la cuantificación de reordena mientos génicos de inmunoglobulinas (Ig) y receptores de linfocitos-T (TCR). Los objetivos del presente trabajo fueron describir los reordenamientos detectados de Ig/TCR, evaluar el efecto de la ERM en la supervivencia de niños con LLA y comparar la ERM por Ig/TCR con la cuantificada mediante citometría de flujo multiparamétrica (CFM). Del total de 455 pacientes estudiados, en el 96% fue posible caracterizar al menos un reordenamiento de Ig/TCR. El total de reordenamientos clonales detectados fue de 1550. La ERM pudo ser estudiada en forma exitosa en el 89% de los casos. El valor de ERM positiva combinada al día 33 y 78 de tratamiento, permitió identificar pacientes de alto riesgo, entre los previamente estratificados por la ERM mediante CFM al día 15. La comparación entre la determinación de ERM mediante reordenamientos Ig/TCR y CFM mostró una excelente correlación. El presente trabajo constituye un estudio de ERM mediante Ig/TCR realizado en un número muy significativo de pacientes diagnosticados en forma consecutiva, tratados en el marco de un protocolo homogéneo y con excelente seguimiento clínico.

Abstract Acute leukemias are the most common neoplasm in pediatric patients. Currently, 80% of children with diagnosis of acute lymphoblastic leukemia (ALL) are cured with conventional chemotherapy, but 20% of them will have a recurrence of the disease. Measurable Residual Disease (MRD) has been described as an important prognostic factor that allows evaluating the response of patients to treatment. One of the most sensitive techniques to study MRD is the quantification of immunoglobulins (Ig) and T-lymphocyte receptors (TCR) genes rearrangements. The aims of this study were to describe the detected Ig/TCR rearrangements, to evaluate the prognostic impact of MRD in our population of children with ALL and to compare the MRD values by Ig/TCR with those obtained by multiparametric flow cytometry (MFC). A total of 455 patients were studied. In 96% of the cases, it was possible to characterize at least one Ig/TCR rearrangement. The total number of Ig/TCR rear rangements detected was 1550. MRD was successfully applied in 89% of the cases. The combined positive MRD values at day 33 and 78 of treatment allow the identification of high-risk patients in cases previously stratified by MRD using flow cytometry at day 15. The comparison between MRD determination by Ig/TCR rearrangements and FC showed excellent correlation. The present work constitutes a study of MRD by Ig/TCR carried out in a very significant number of patients consecutively diagnosed, treated within a homogeneous protocol and with excellent clinical follow-up.

Tratamiento de la leucemia mieloblástica aguda con translocación (8; 21) en Hospital Base Valdivia: ejemplificado en un caso clínico / Management and follow-up of acute myeloblastic leukemia with translocation (8; 21): report of one case

We describe the management and follow-up of a 20-year-old male with acute myeloblastic leukemia with translocation (8; 21) [t (8; 21)]. A quantitative polymerase chain reaction for t(8; 21) in bone marrow was performed at diagnosis and after three consolidations with high doses of cytarabine. Currently, the management of this type of leukemias has been oriented towards the early detection of relapse. The concept of minimal or measurable residual disease, as the burden of leukemia cells that persist undetected, is an important tool in the therapeutic decision and follow-up of these patients.

Residual disease after operative hysteroscopy in patients with endometrioid endometrial cancer associated with polyps / Doença residual após histeroscopia cirúrgica em pacientes com câncer de endométrio endometrioide associado a pólipo endometrial

Abstract Objective To evaluate the presence of residual disease in the uterine specimen after hysteroscopic polypectomy or polyp biopsy in patients with endometrioid endometrial cancer (EC). Methods We analyzed a series of 104 patients (92 cases from the Hospital AC Camargo and 12 from the Hospital do Servidor Público Estadual de São Paulo) with polyps that were diagnosed by hysteroscopy, showing endometrioid EC associated with the polyp or in the final pathological specimen. Patients underwent a surgical approach for endometrial cancer from January 2002 to January 2017. Their clinical and pathological data were retrospectively retrieved from the medical records. Results In78cases (75%), thepolyphad EC, and in 40(38.5%), itwas restricted tothe polyp, without endometrial involvement. The pathologic stage was IA in 96 cases (92.3%) and 90 (86.5%) had histologic grade 1 or 2. In 18 cases (17.3%), there was no residual disease in the final uterine specimen, but only in 9 of them the hysteroscopy suggested that the tumor was restricted to the polyp. In 5 cases (4.8%) from the group without outside of the polyp during hysteroscopy, myometrial invasion was noted in the final uterine specimen. This finding suggests the possibility of disease extrapolation through the base of the polyp. Conclusion Patients with endometrioid EC associated with polyps may have the tumor completely removed during hysteroscopy, but the variables shown in the present study could not safely predict which patient would have no residual disease.

Resumo Objetivo Avaliar a presença de doença residual no exame anatomopatológico definitivo de pacientes com câncer de endométrio endometrioide após polipectomia ou biópsia de pólipo histeroscópica. Métodos Analisamos 104 pacientes (92 casos do Hospital AC Camargo e 12 casos do Hospital do Servidor Público Estadual de São Paulo) com pólipos diagnosticados durante histeroscopia e cuja biópsia histeroscópica ou exame patológico final do útero acusaram câncer de endométrio endometrioide. As pacientes foram submetidas a cirurgia para câncer de endométrio de janeiro de 2002 a janeiro de 2017. Os dados clínicos e anatomopatológicos de cada paciente foram retirados dos prontuários médicos Resultados Em 78 casos (75%), o pólipo continha a neoplasia, e em 40 (38.5%), ela estava restrita ao tecido do pólipo, sem envolvimento endometrial adjacente. O estadio final foi IA em 96 casos (92.3%) e em 90 (86.5%) tratava-se de grau 1 ou 2. Em 18 casos (17.3%), não havia doença residual no espécime uterino, mas emapenas 9 deles a histeroscopia sugeriu doença restrita ao pólipo. Em 5 casos (4.8%), não havia doença aparente extrapólipo na histeroscopia, mas havia invasão miometrial, sugerindo extravasamento do tumor pela base do pólipo. Conclusão Pacientes com câncer de endométrio associado a pólipos podem ter o tumor completamente removido durante a histeroscopia, mas, com as variáveis avaliadas, é difícil predizer com segurança qual paciente ficará sem tumor residual.