Acute Nonlymphoblastic Leukemia Research Articles

Acute Non-Lymphoblastic Leukemias Presenting with Gingival Hyperplasia: Diagnosis and Management Updates

Background: Leukemias represent a heterogeneous group of hematological malignancies, which are characterized by the disordered proliferation of neoplastic hematopoietic cells, with the diffuse bone marrow involvement. Most frequent oral findings in leukemias are cyanotic or erythematous gingival hyperplasia with or without necrosis, petechiae, ecchymoses, mucosal ulcers and hemorrhage. Gingival hyperplasia is reported as a consistent symptom, which forwards patients for a dentistry consultation, that may lead to an early diagnosis of acute leukemias. The recognition of gingival enlargement as an initial oral manifestation of leukemic involvement assumes major practical significance, especially for the early diagnosis of non-lymphoblastic leukemias. Objectives: The aims of researches were the evaluation of diagnosis and management of hyperplastic gingivitis in acute leukemias. Material and Methods: The patients' follow-up and treatment were realized at the comprehensive cancer center. Our observational, analytical and descriptive study enrolled 8 patients with acute leukemias, who were treated at the Institute of Oncology from Moldova between 2012-2023. The diagnosis was asserted by the bone marrow aspiration with cytochemical reactions, tissue biopsy, buccal swab, or fine needle aspiration cytology. The immunophenotyping was performed in selected cases. The types of acute leukemias were assessed and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This prospective study was related to the hospitalized and outpatient care. Results: Hyperplastic gingivitis developed in cases with myelomonocytic and monocytic acute leukemias. The leukemia patients were admitted to the Institute of Oncology with a history of fatigue, fever, bone pain, gingival bleeding and enlargement detected by dentistry and family doctors from the consulting centers. ECOG-WHO performance score was 2-3. The intra-oral examination revealed generalized gingival hyperplasia. There were the amounts of plaque and calculus, which did not justify the enlargement degree. The gingiva was spongy and painless on palpation, with solitary sectors of necrosis and mucosal bleeding. Multiple soft and tender lymph nodes ranging from 0.8-1.5 cm in diameter were palpable bilaterally in the cervical and axillary regions. Splenomegaly of various degree was revealed by ultrasound scan in all patients. Complete blood count values ranged between: Hb 66-104 g/l, RBC 2.3-3.7 x 10 12/l, WBC 11.3-47.2 x 10 9/l, PLT 17.0-115.0 x 10 9/l, blast cells 17-65%. The bone marrow aspiration detected hypercellularity, myeloid and monocytic blast cells (31.0-58.0%), as well as monocytes (9.0-14.0%). The studied cases were not suggestive of presence of FLT3 mutations. Hyperplastic gingivitis regressed in 5 (62.5%) cases after the achievement of complete (4 patients) and partial (1 patient) hematological responses under the first-line combined chemotherapy with conventional doses of cytarabine, anthracyclines and etoposide (2 patients). Local treatment included daily administration of oral steroids, antiseptic and hemostatic drugs. The narrative review of the recent references revealed that 37-53% of patients with monocytic and myelomonocytic leukemias were reported to develop gingival hyperplasia. Conclusions: Hyperplastic gingivitis emerges in acute leukemias mostly due to the gingival infiltration with neoplastic blast cells. Gingival hyperplasia may regress under the combined chemotherapy and local treatment in patients with complete or partial hematological responses. Early diagnosis and treatment, thus, can increase the leukemia patients' prospects for complete hematological and local responses.

Change of ABO blood group in a patient with Acute Myelocytic Leukemia (AML): a case report

Background: ABO and Rhesus blood groups are clinically important, especially in blood transfusion. Blood groups are determined by the antigens found on the erythrocyte membrane. In patients with hematologic malignancies, especially from the myeloid lineage, changes in blood group can occur in the ABO system mainly due to weakness or loss of some ABO antigens. Case Description: A nine-year-old girl was admitted to the hospital with a chief complaint of high fever three days before admission. The patient had been diagnosed with acute non-lymphoblastic leukemia three months ago. From medical history, the patient had undergone chemotherapy and received 22 bags of PRC transfusion with blood group O (+) from February 27th until May 28th 2018. On July 21st 2018, the transfusion procedure was repeated, and the blood group showed B (+). The procedure was repeated using a new sample but the result remained the same. The crossmatch was performed with five blood groups O (+) and two blood groups B (+) showed mayor: negative, minor:+weak, AC:+weak, mayor: negative, minor:+weak, AC:+weak, respectively. Conclusion: Changes in blood group antigens in hematologic malignancies that experience ABO antigen alternation and return to the original blood group reflect the remission from the disease. The expression of H antigen in blood groups A and B may revert to normal with an improvement from the underlying disease.

Analyzing sleep status in children with acute leukemia

BackgroundQuality sleep is essential for physical and mental health. We aimed to analyze sleep disorders in children with acute leukemia and explore associated factors.MethodsGeneral data and sleep disorders in children with acute leukemia during chemotherapy were collected by general questionnaires, Children's Sleep Disorders Scale and the Parenting Stress Index-short form.ResultsIn total, 173 valid questionnaires were collected. The total Sleep Disorder Scale score > 39 is considered a sleep disorder, while sleep disorders accounted for 45.66% (79/173). In the cohort, 167 children had acute lymphoblastic leukemia, with 40.12% (67/167) having sleep disorders, while six children had acute non-lymphoblastic leukemia, with 50.00% (3/6) having sleep disorders. Single- and multi-factor regression analyses of age, gender, number of children in the family, and time spent using electronic devices showed that factors influencing sleep disorders in these children were mainly parental scolding and adenoid hypertrophy. Children with sleep disorders had more parental stress than those without sleep disorders (P < 0.05).ConclusionsThe high incidence of sleep disorders in children with acute leukemia is related to airway conditions and parental behaviors. Sleep disorders in children can increase parenting stress. Factors potentially affecting sleep quality should be addressed as early as possible, while parental education should be strengthened to better facilitate the physical and psychological recovery of their children.

Clinical Observation on 98 Cases of Hematological Malignancies Treated with Autologous Hematopoietic Stem Cell Transplantation Cryopreserved By Ladder-Style Freezing from Low Temperature Refrigerator to Liquid Nitrogen

Background: Programmed cooling - 196℃ liquid nitrogen preservation and non- programmed cooling - 80℃ low temperature refrigerator preservation have been widely used in Auto- HSCT. Programmed cooling and - 196℃ liquid nitrogen preservation can set the rate of temperature fall in advance and standardize the cooling process, reducing the damage to hematopoietic stem cells caused by temperature fall. But programmed cooling is a time-consuming process and it needs to purchase expensive control rate freezer. Non- programmed cooling - 80℃ low temperature refrigerator preservation is easy to operate, but it cannot keep a long preservation period. Since 2002, we tried combining two preservation methods into one: first we placed freezer bags in - 80℃ low temperature refrigerator and then placed them in -196℃ liquid nitrogen tank for long-term preservation, with the purpose of prolonging the cryopreservation of stem cells.Method:We observed the influence of cryopreservation of hematopoietic stem cells with ladder-style freezing from low temperature refrigerator to liquid nitrogen in transplantation treatment of hematological malignancies, and analyzed the survival condition of patients after hematopoietic stem cell transplantation.We retrospectively analyzed the clinical datas of 98 patients with hematological malignancies treated by hematopoietic stem cell transplantation from 2002-01 to 2016-12 in our center.Results: 98 patients, 56 males and 42 females, aged 14-69 years (avenge age36.46±14.19 years). Disease subtypes: 10 cases of acute lymphoblastic leukemia(ALL), 24 cases of acute non- lymphoblastic leukemia(ANLL) , 11 cases of multiple myeloma(MM), 53 cases of malignant lymphoma(ML). One case failed in implantation due to intracranial hemorrhage and the other 97 cases all succeeded in hematopoietic reconstitution. The median survival time was 47 months and the average follow-up time was 50.11 months. The average time needed to neutrophil count ≥0.5×109/L was 9.24±1.89d, and the average time needed to platelet count≥20×109/L without platelet transfusion for 3 days was 11.04±1.84d. The median survival time was 47.6 months (1~80 months). The overall survival rates of 1 year, 3-year and 5-year were (97.2±1.9) %, (84.2±4.6) % and (77.8±5.6) %, respectively. PFS (progression-free survival) of patients in 3 years and 5 years were (74.4±5.1)% and (61.2±6.2)% (Figure1), which is consistent with data reported by other transplantation centers. In this study, it is found that the application of auto-HSCT has significantly improved OS and PFS of patients with acute leukemia, malignant lymphoma and multiple myeloma, but there is no significant difference in OS and PFS among three groups(Figure2)(P=0.537). The survival condition of CR1 patients was better than no-CR1 patients(Figure3). The complication about transplantation mainly were digestive tract symptoms. 9.18% patients complicated with liver function injury and 58.16% patients got infection.We continuously improved cryophylactic agent and obtained cryoprotectant formed by 3%hydroxyethyl starch, 4% albumin and 5% DMSO to replace the traditional 10% DMSO cryoprotectant used in programmed cooling. During stem cell infusion, the occurrence rate of complication was 8.16%, significant lower than the occurrence rate of adverse events occurring in the usage of 10% DMSO cryoprotectant.Conclusions: ladder-style freezing from low temperature refrigerator to liquid nitrogen with cryoprotectant that is formed by 3% hydroxyethyl starch, 4% albumin and 5% dimethyl sulfoxide (DMSO) for cryopreservation of hematopoietic stem cells. It can reach the same clinical transplantation effect with traditional programmed cooling freezing method in autologous hematopoietic stem cells transplantation (auto-HSCT) and can effectively improve OS, PFS of hematological malignancies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Intensive Treatment of Children With Acute Lymphoblastic Leukemia According to ALL-BFM-86 Without Cranial Radiotherapy: Results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991)

AbstractIn The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et al, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on leukemia cell mass and response to initial treatment: standard-risk group (SRG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a randomized study on late intensification (protocol S) was performed in RG patients, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65.3% (standard error [SE] 3.2%), which was significantly different from the 73% (SE 1%) 5-year EFS achieved in the ALL-BFM-86 study (P = .02, Z-test). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates were 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant difference could be established (P = .67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12.0%), respectively. SRG patients receiving protocol II fared better than patients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54.5% [SE 7.5], respectively). No difference in 5-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CNS relapses occurred in SRG patients receiving protocol II. Six children died in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective method of CNS prophylaxis in the context of BFM-oriented treatment for all children with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DCLSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early reinduction with protocol II is essential in the treatment of SRG patients and that late intensification with protocol S does not improve the prognosis for RG patients.

Acute Non Lymphoblastic Leukemia in the Department of Child Health School of Medicine, University of North Sumatera/ Dr. Pirngadi Hospital Medan (1983-1988): A Preliminary Study

A retrospective study on Acute Non Lymphoblastic Leukemia (ANLL) was conducted at the Sub Division of Pediatric Hematology, School of Medicine, University of North Sumatera/Dr. Pirngadi Hospital Medan, in a period of 5 years (1983-1988). There were 18 cases consisted of 14 (77.78%) males and 4 (22.22%) females with the age group of 0-2 years: 6 (30%), 2-8 years: 9 (50%), 8-15 years: 3 (30%). By the FAB classification, they were of FAB M-1: 1 (5.55%). FAB M-2: 1 (5.55%), FAB M-3: 1 (5.55%), FAB M-4: 2 (11.12%) and FAB M-6: 13 (72.23%). Only 7 (38.88%) were treated with cytostatics while the others received only supportive therapy. The result of cytostatic treatment was unsatisfactory: 4 (57.14%) died within the first 2 months of treatment, 3 (42.86%) discontinued their cytostatics treatment.

Peripheral Neuropathy in Patients with Acute Leukemia Treated with Vincristine

Between December 1993 and December 1994, 46 patients with acute leukemia treated with vincristine were evaluated for the possibilities of peripheral neuropathy. Of the 46 patients, 39 patients had acute lymphoblastic leukemia, and 7 had acute non-lymphoblastic leukemia. All patients had received vincristine; 29 (63%) of the 46 patients had it for 5 - 9 weeks, and 17 (37%) had it for 4 weeks or less. rn 10 (21.7%) patients peripheral neuropathy was detected clinically, and in 35 patients (76%) the neuropathy was detected by electrodiagnostic examination. No evidence of neuropathy was detected in 11 patients. The electrodiagnostic examination was more sensitive than the clinical examination. Pe1ipheral neuropathy, either detected clinically or by means of electromyography, occurred mostly in patients with the dosage of vincristine of 5-20 mg, and the duration of treatment of 5-9 weeks.

Cisplatin. Documentation of proposed values of occupational exposure limits (OELs)

Cisplatin. Documentation of proposed values of occupational exposure limits (OELs)

Stan zdrowia, płodność i potomstwo oraz sytuacja socjoekonomiczna osób po leczeniu choroby nowotworowej układu krwiotwórczego w dzieciństwie

IntroductionThe comprehensive cancer treatment increased the curability and long-term remission of malignant tumors in children. When assessing the results of treatment, one should be aware of long-term complications of anticancer therapy. The aim of this study is to present health status, socioeconomic situation, the aspect of fertility and offspring in patients treated for hematologic malignancies in childhood. Materials and methodsAnalysis of medical records of patients hospitalized at the Department of Pediatric Hematology and Oncology Medical University of Silesia in Katowice between 1986 and 2004, treated for acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, Hodgkin and non-Hodgkin lymphoma. Up to 160 individuals over 26 years were sent a covering letter with a survey on the health, socioeconomic status and offspring. 32 responses were obtained. Results60% of respondents define their current state of health as average, 40% as good. 70% do not require constant care of specialist. Chronic diseases occurred in 26.67% of patients. Most of the respondents deny stimulants. 90% of patients are physically active. 60% had no educational problems. 96.7% completed high or secondary education; 93.33% are professionally active. The majority of respondents are married or in a partnership. 13.33% of the respondents experienced fertility problems. 43.33% patients have children. In 81.25% cases pregnancy was uncomplicated. The status of newborns was defined mostly as very good. ConclusionsLate health complications occur in people treated for neoplastic disease in childhood. No influence of former neoplastic disease on psychosocial functioning or status and growth of offspring was noticed.

Therapy-related myelodysplastic syndrome/acute leukemia after multiple myeloma in the era of novel agents

Survival for patients with multiple myeloma has increased. Both melphalan and lenalidomide are associated with subsequent development of myelodysplasia. We reviewed the cases of all patients with multiple myeloma who had subsequent development of myelodysplastic syndrome (MDS) or acute non-lymphoblastic leukemia (ANLL) during a 12-year period in three centers. Of 55 patients identified, two received only lenalidomide before myelodysplasia developed. The median time between the diagnoses of multiple myeloma and MDS/ANLL was 52.7 months. Median survival after the diagnosis of MDS or ANLL was 6.7 months. Treatment of MDS comprised allogeneic stem cell transplant in eight patients (median survival, 219 days; one patient alive at 624 days) and a hypomethylating agent in 21 patients (response of stable or better in five patients). Myelodysplasia remains a devastating complication of therapy for multiple myeloma, with short survival and poor response rates to available modalities.

Childhood cancer incidence and survival 1985-2009, Khon Kaen, Thailand.

The Khon Kaen Cancer Registry (KKCR) was established in 1984. Previous population-based incidences and survivals of childhood cancer in Thailand were determined using a short cancer registration period. Data were retrieved of all children residing in Khon Kaen, between 0-15 years, diagnosed as having cancer and registered in the KKCR (1985-2009). The follow-up censored date was December 31, 2012. The childhood cancers were classified into 12 diagnostic groups, according to the International Classification of Childhood Cancer. The incidence was calculated by the standard method. Survival of childhood cancer was investigated using the KKCR population-based registration data and overall survival calculated using the Kaplan Meier method. In the study period, 912 newly diagnosed cases of childhood cancer were registered. The respective mean and median age was 6.4 (SD=4.6) and 6 (0-14) years. The age-peak for incidence was 0-4 years. The age-standardized rate (ASR) was 83 per million. Leukemia was the most common cancer (N=360, ASR 33.8) followed by neoplasms of the central nervous system (CNS, N=150, ASR 12.8) and lymphoma (N=79, ASR 7.0). The follow-up duration totaled 101,250 months. The death rate was 1.11 per 100 person-months (95%CI: 1.02 -1.20). The 5-year overall survival was 52% (95%CI: 53-56.9) for all cancers. The respective 5-year overall survival for (1) acute lymphoblastic leukemia (ALL), (2) acute non-lymphoblastic leukemia (ANLL), (3) lymphoma, (4) germ cell tumors, (5) renal tumors, (6) retinoblastoma, (7) soft tissue tumors, (8) CNS tumors, (9) bone tumors, (10) liver tumors, and (11) neuroblastoma was (1) 51%, (2) 37%, (3) 63%, (4) 74%, (5) 67%, (6) 55%, (7) 46%, (8) 44%, (9) 36%, (10) 34%, and (11) 25%. The incidence of childhood cancer is lower than those of western countries. Respective overall survival for ALL, lymphoma, renal tumors, liver tumors, retinoblastoma, soft tissue tumors is lower than that reported in developed countries while survival for CNS tumors, neuroblastoma and germ cell tumors is comparable.

Metachronous bilateral granulocytic sarcoma of the testis in a young adult: a report of an unusual entity.

Granulocytic sarcomas are rare tumors composed of neoplastic blood cells, typically occurring during the course of acute nonlymphoblastic leukemia or before its onset. We present a case of a 23-year-old young adult man with metachronous granulocytic sarcoma of the testis without hematologic manifestations who was diagnosed with granulocytic sarcoma (GS). The patient was treated with right orchiectomy but relapsed with a left testicular mass 16 months later when a left orchiectomy was performed. The patient has been free of disease for 13 months following the left orchiectomy. This case highlights a rare hematologic cancer that urologists and pathologists should be aware of since it can present as a testicular mass. Only 3 cases of testicular GS without an associated hematologic disorder have been described. To the best of our knowledge, our patient is the first reported case in the English literature of metachronous GS of the testis with no evidence of hematologic disorder.

THE Analysis of CEBPA, NPM1, FLT3 and P53 gene mutations in groups of patients with myelodysplastic syndrome and acute nonlymphocytic leukaemia

The article presents the molecular genetic analysis of the prevalence of somatic mutations in FLT3, NPM1, CEBPA, and p53 genes in a group consisting of 23 patients with myelodysplastic syndrome MDS (option - refractory anemia with excess blasts, RAEB) and 97 patients with acute nonlymphoblastic leukemia (ANLL). It was ascertained that FLT3-ITD mutations in the group of patients with MDS RAEB occur with the prevalence of 8,7 ± 5,9 %, while in the group with ANLL they are observed in 22,7 ± 4,3 % cases. FLT3 D835 mutations were detected only in the ANLL group with the prevalence of 7.2±2.6 %. NPM1 gene mutations were detected in 8,7 ± 5,9 % of MDS RAEB cases and in 21,6 ± 4,2 % of ANLL cases. CEBPA somatic mutations were found in 11,3 ± 3,2 % of ANLL cases, while the group of MDS RAEB was free of them. Mutations in the p53 gene were detected in 17,4 ± 7,9 % of MDS RAEB cases and in 10,3 ± 0,3 % of ANLL cases. All the detected CEBPA and p53 gene mutations were described by means of direct sequencing. The analysis results show that the use of molecular genetic markers in combination with cytogenetic ones makes it possible to expand the group with prognostic markers by 41,3 % in comparison with the use of only cytogenetic data.

Association of HLA -A, -B and -DRB1 alleles with hematological diseases in Vojvodina

Major histocompatibility complex (MHC) genes are involved in various mechanisms of pathogenesis and immunoediting of hematological diseases. This study aimed to investigate the association between HLA -A, -B and -DRB1 alleles with hematological diseases. In this study, we performed DNA-based HLA typing by polymerase chain reaction analysis with sequence-specific primers (PCR-SSP) to distinguish HLA-A, -B, and -DRB1 alleles. Eighty-two patients with hematological diseases (29 with acute lymphoblastic leukemia (ALL), 19 with acute nonlymphoblastic leukemia (ANLL), 5 with chronic myelogenous leukemia (CML), 2 with chronic lymphocytic leukemia (CLL), 9 with myelodysplastic syndrome (MDS), 9 with lymphomas (M.Hodgkin (HL) and non-Hodgkin (NHL)), 7 with aplastic anemia (AA) and 2 with multiple myeloma (MM)), were included in the study and compared with 111 healthy blood donors, residents from Vojvodina, evaluating the strength of the observed associations by measuring the aetiologic and preventive fractions. Among the alleles significantly associated with hematological diseases, HLA-A*24 showed an aetiologic fraction higher than those of HLA-A*26 and A*25 (RR=1.027, EF=1.233, RR=1.047, EF=1.141 and RR=1.213, EF=0.910).Negative association with significant preventive fraction was observed with HLA-B*18 and HLA-DRB1*11 alleles, with RR=0.400, PF=0.179 and RR=0.587, PF=0.176. Our results suggest that HLA-A*24, A*26 and A*25 as associated more frequently than other specificities with a hypothetical disease predisposing genes, may play a role in the pathogenesis of hematological diseases.

Leptin promoter G–2548A genotypes and associated serum leptin levels in childhood acute leukemia at diagnosis and under high-dose steroid therapy

Genotype/allele distributions of leptin promoter G−2548A polymorphism, serum leptin and insulin levels and body weight were not significantly different between 72 children (39 male/33 female; age range 1.08–16, median 6 years) with acute leukemia (56 acute lymphoblastic leukemia [ALL]/16 acute non-lymphoblastic leukemia [ANLL]) at diagnosis and 70 age- and sex-matched controls (p > 0.05). The − 2548GG genotype was associated with the highest leptin levels in controls and patients with acute leukemia after 7-day high-dose methylprednisolone (HDMP) therapy (p < 0.05), while no significant association of genotype with leptin levels was detected in patients at diagnosis (p > 0.05). One-week HDMP therapy in patients carrying the − 2548G allele caused a significant increase in leptin levels and body weight (p < 0.001), whereas increases in those carrying the − 2548AA genotype were insignificant (p > 0.05). Decreases in white blood cell counts of patients after therapy were insignificant in − 2548GG (p > 0.05) yet significant in − 2548GA and − 2548AA (p < 0.05) genotypes. These results revealed no association of leptin genotype with the etiology of childhood acute leukemia but a possible association with leptin levels and effects of HDMP therapy.

Individualized Tumor Response Testing (ITRT) Profile Has a Prognostic Value in Childhood Acute Lymphoblastic Leukemia (ALL) and Acute Non-Lymphoblastic Leukemia (ANLL): The Multicenter Non-Interventional Long-Term Follow-up Study of Polish Pediatric Leukemia Study Group

Abstract 1456▪▪This icon denotes a clinically relevant abstract BACKGROUND:Individualized tumor response testing (ITRT) is a recently accepted term for ex vivo drug resistance profile testing in cancer patients. Previous studies have shown that ITRT results in children correspond with clinical response in initial acute lymphoblastic leukemia (iALL), but not in initial acute myeloid leukemia (iAML). ITRT combined profile to prednisolone, vincristine, and L-asparaginase (PVA score) showed a strong association with clinical outcome in iALL (Den Boer et al JCO; Hollemann et al, NEJM). OBJECTIVE: Polish Pediatric Leukemia Study Group carried out between 1999–2010 a multi-institutional, non-interventional study on correlation between ITRT profile and clinical response in long-term follow-up. The objective of the study was to assess the role of ITRT profile as prognostic factor in childhood iALL and iAML. MATERIALS AND METHODS: A total number of 998 children (median age 6.5 yrs, range 3 days - 21 yrs) were enrolled into the study, including 817 with initial ALL (iALL) and 181 children with initial AML (iAML). The median follow-up was 4.6 yrs (range 0–10,4). ITRT (ex vivo drug resistance profile) was determined by the MTT assay. Following drugs were tested: prednisolone (P), vincristine (V), L-asparaginase (A), daunorubicin (D), doxorubicin (Dox), idarubicin (I), mitoxantrone (M), cytarabine (C), busulfan (B) and etoposide (E). Apart from ITRT to single drugs, combined ex vivo drug resistance profiles PVA, PVADC, PVADoxC in iALL and CVIDM in iAML were also determined. Probability of DFS was estimated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed in Cox regression model. RESULTS: (1) For iALL patients, neither single drug nor 3-drugs PVA combined ITRT profile had prognostic value for pDFS. 5-drug PVADC and PVADoxC profiles had predictive values, with p-values 0.049 and 0.017, respectively. For 295 iALL patients with ITRT-sensitive PVADC profile, 5-year pDFS=0.892. No ITRT factor was discriminative between very early, early and late ALL relapses. In univariate analysis in Cox model, following factors had prognostic value for pDFS in iALL: steroid resistance by day 8 (p=0.002), bone marrow (BM) response by day 15 (p=0.005), BM response by day 33 (p=0.001) and PVADC ITRT profile (p=0.052). In multivariate analysis in Cox model, only BM response by day 33 (p=0.001) had prognostic value for pDFS in iALL, while bone marrow BM by day 15 had borderline significance (p=0.055). (2) For iAML patients, ITRT to cytarabine had an impact on pDFS (0.81 vs 0.63, p=0.047). For 55 iAML patients with ITRT-sensitive to cytarabine, 5-year pDFS=0.816. 5-drug CVIDM profile had also predictive values, with p-value 0.020. No ITRT factor was discriminative between very early, and late AML relapses. In univariate analysis in Cox model, no factor had prognostic value for pDFS in iAML, while ITRT to cytarabine almost reached significance (p=0.054). Multivariate analysis for iAML was not performed. CONCLUSION: Ex vivo drug resistance profile (ITRT) can be regarded as a risk factor in childhood acute leukemias. Combined ITRT profile to prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine (PVADC) has predictive value in pediatric iALL, while ITRT profile to cytarabine has prognostic value in pediatric iAML. ACKNOWLEDGEMENTS: Supported by grants: EFS-POKL.04.01.01-00-191/08-00 nr 1/2010; MNiSW Nr N N407 541339; MNiSW Nr N407 078 32/2964; UMK 09/2009; UMK 10/2009. Disclosures:No relevant conflicts of interest to declare.

MUTATIONAL ANALYSIS OF FLT3 AND NPM1 GENES IN THE GROUP OF ADULT PATIENTS WITH MYELODYSPLASTIC SYNDROME AND ACUTE NON-LYMPHOBLASTIC LEUKEMIA

The molecular-genetic analysis of DNA samples extracted from the blood and marrow of 14 patients with myelodysplastic syndrome (refractory anemia with excess blasts) and 52 patients with acute non-lymphoblastic leukemia has been performed. It did not reveal any clinically unfavourable mutations of FLT3 gene in the group of the patients with myelodysplastic syndrome. The frequency rates for FLT3-ITD, FLT3 D835 and NPM1 mutations in the group of the patients with acute non-lymphoblastic leukemia made up 21,2 ± 5,7; 5,8 ± 3,2 and 23,1 ± 5,8 per cent, correspondingly. The subgroup of the patients with acute promyelocytic leukemia (М3) detected more FLT3-ITD mutations while the subgroup with acute myeloblastic leukemia (М1) had more NPM1 gene mutations (most of the cases in association with FLT3-ITD mutation). It was shown that a more sensitive genetic test required the use of both blood and marrow DNA samples.

Serine protease (TPS): A diagnostic and prognostic marker in pediatric patients with acute non-lymphoblastic leukemia

The Serine protease, TPS (tryptase), is a specific marker for mast cells and mast cell-associated disorders. However, substantial amounts of TPS are also expressed in neoplastic myeloid, non-mast cell lineage. The aim of this study is determination and quantitation of TPS expression in patients with acute non-lymphoblastic leukemia (ANLL); to evaluate its prognostic value and its relevance as a genetic marker for detection of minimal residual blast cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect levels of TPS from 30 newly diagnosed ANLL children and 10 normal children served as controls. TPS levels for positive cases were reevaluated after induction chemotherapy; after onset of relapse or by the end of the study. Our results showed that the gene transcripts were detected in 56.7% of patients but were not expressed by normal controls. The highest frequency of TPS was recorded in patients with M4 showing significantly higher levels compared to other FAB (French–American–British Classification) subtypes. TPS levels were directly correlated to TLC, absolute blast counts in peripheral blood, levels of CD34 and CD117. After induction chemotherapy, levels of TPS decreased significantly in those who achieved complete remission while it increased significantly in relapsed patients, with a risk estimate of relapse six times higher in positive cases than TPS negative patients. 84.6% of the patients negative for TPS achieved complete remission with better disease free survival. In conclusion, TPS is expressed in a group of patients with ANLL thus serves as a disease related marker; it could be used as a prognostic indicator in evaluating remission status and early relapse as its elevated levels are associated with high risk of relapse; again, it is useful in predicting disease outcome.

Myeloid sarcoma of the upper extremity causing compartment syndrome: a case report

Myeloid sarcoma, also known as chloroma, granulocytic sarcoma, or myeloblastoma, is a rare, solid neoplasm comprised of immature extramedullary granulocytic cells, seen most frequently as a manifestation of myeloid leukemia. It often occurs either as the presenting symptom of leukemia, or as the harbinger of leukemia to come several months later, developing at some point in the disease course of 2% to 8% of patients with acute nonlymphoblastic leukemia overall. When occurring in patients without overt systemic signs of leukemia, the average time to the development of systemic disease is less than 1 year.1,2 Common sites of disease include the soft tissues, skin, bone, and lymph nodes. Less commonly, myeloid sarcoma can be seen in the intestines, mediastinum, epidural space, uterus, or ovary.3-6 Myeloid sarcoma presenting in the extremities is extremely rare. In this report we detail the unusual presentation of a compartment syndrome as the index presentation of a myeloid sarcoma in the soft tissues of the upper extremity.

小児再発ANLLに対する大量cytosine arabinoside, mitoxantrone (HAM) 併用療法

小児再発ANLLに対する大量cytosine arabinoside, mitoxantrone (HAM) 併用療法