Therapy Related Acute Myeloid Leukemia in Solid Tumors: Two Pediatric Case Reports and Review of the Literature

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Bodour Elhussein ◽  
Ebtsam Alhariri ◽  
Amal Najm ◽  
Walid Ibrahim ◽  
Ghaleb Elyamany ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Local Recurrence ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Case Reports ◽  
Alkylating Agents ◽  
Bone Marrow Aspiration ◽  
Secondary Malignancy ◽  
Acute Myeloid

Introduction: Therapy-related acute myeloid leukemia is devastating late effects in solid tumors. The most frequent and lethal secondary malignancy is secondary acute myeloid leukemia t-AML. t-AML is a sequel of specific chemotherapeutic agents, specifically alkylating agents, and topoisomerase II inhibitors, commonly used in treating solid tumors. t-AML is relatively rare with a poor prognosis. Case reports: We are reporting two cases of t-AML. Case 1: A 13-year-old girl presented with left hand swelling in 2014. Biopsy confirmed the diagnosis as Ewing sarcoma. She started a chemotherapy regimen that contained alkylating agents and epipodophyllotoxins. In 2017, local recurrence occurred, and she received salvage chemotherapy (ifosfamide, carboplatin, and etoposide) followed by amputation of the left 4th finger. In 2020, she had a second local recurrence with unexplained prolonged neutropenia. Diagnosis of t-AML was confirmed by bone marrow aspiration. Case 2: A 5-years-old boy presented with an abdominal mass in July 2006. It was diagnosed as rhabdomyosarcoma and treated with alkylating agents. He showed a good response to the treatment initially. In September 2007, prolonged pancytopenia, neutropenia, and thrombocytopenia occurred. Diagnosis of t-AML was confirmed by bone marrow aspiration as it showed mild dysplastic, moderate marrow fibrosis. Conclusion: t-AML is of growing interest to the pediatric oncologist and requires further studies to develop pathways for leukemogenesis. We discussed two cases to highlight the importance of designing treatment regimens for solid tumors associated with t-AML.

Prognostic and Therapeutic Value of Day 14 Bone Marrow Aspiration in Adult Acute Myeloid Leukemia Patients

2019 ◽  
Vol 19 (7) ◽  
pp. e406-e413
Author(s):  
Mosaad M. El Gammal ◽  
Hend M. Owaidat ◽  
Reham A. Rashed ◽  
Raafat Abdel Fatah ◽  
Mohamed A. Samra
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Aspiration ◽  
Therapeutic Value ◽  
Acute Myeloid

Bone Marrow Small Adipocytes in Acute Myeloid Leukemia Correlate with Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2874-2874
Author(s):  
Wei Lu ◽  
Jun Shi
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Biopsy Specimens ◽  
Brown Adipose ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Introduction: Adipocytes have a substantial effect on the outcome and progression of certain solid tumors. However, little attention has been paid to the role of bone marrow (BM) adipocytes in acute myeloid leukemia (AML) because it is difficult to observe adipocytes through clinical BM aspiration. Although it was reported that adipocytes affected the behavior of leukemia cells in vitro, there is still no direct in vivo evidence. In the present study, we investigated the influence of adipocytes by focusing on their changing size in BM from primary AML patients. Methods: We retrospectively analyzed the biopsy specimens of BM from 70 patients with newly diagnosed AML and 70 controls with lymphoma or solid tumors without infiltration of BM. The size and type of adipocytes were analyzed for average diameter (Ad.Dm) and area (Ad.Ar) by tracing each individual adipocyte with Image-Pro Plus 5.1. Then, AML patients were further divided into 32 patients with continuous complete remission and 38 patients who were refractory based on the treatment effects. Adipocyte number (Ad.N; per square millimeter) and the percentage of adipocyte volume per tissue volume (Ad.V/TV) were compared between these two groups. Furthermore, the prognostic impact of adipocytes on the overall survival (OS) and relapse-free survival (RFS) in AML patients was analyzed by Cox regression analysis and Kaplan-Meier curves. Finally, the phenotype of adipocytes was determined by immunohistochemistry of UCP-1 and Perilipin1 to further explore the possible mechanism of the effect of adipocytes on the prognosis. Results: The Ad.Dm and Ad.Ar in BM from AML patients were 38.3±14.7 µm and 559.4±271.9 µm2, respectively, and both values were significantly smaller than those for the controls (P<0.001). The Ad.Dm exhibited no relation to the number of blasts in BM, indicating that the decreased size of adipocytes in AML cannot be attributed to extensive marrow blasts. Adipocytes were classified as small, medium and large adipocytes according to the frequency distribution of Ad.Dm in BM from controls. A significant difference was detected only in the proportion of small adipocytes (Ad.Dm<42.6 µm) between AML patients and controls (43.9% vs 25%, P=0.005). Furthermore, the Ad.V/TV and Ad.N of the adipocytes in the refractory group were 6.70±3.18% and 31.56±11.72/mm2, respectively, which were significantly higher than those of the remission subjects (P<0.001). This outcome prompted us to further analyze the role of small adipocytes in AML. Patients with Ad.V/TV of small adipocytes≤ 2.3% exhibited a longer OS than patients with Ad.V/TV of small adipocytes >2.3% (P<.001). Similarly, the subjects with Ad.N of small adipocytes <10.6/mm2 (P<.001) had a longer OS. Meanwhile, for the remission AML patients, those with Ad.V/TV of small adipocytes ≤2.5% had a shorter RFS than patients with Ad.V/TV of small adipocytes >2.5% (P<.001), and similar significant differences were also found between patients with Ad.N of small adipocytes ≥9.2/mm2 and Ad.N of small adipocytes <9.2/mm2(P<.001). In the biopsy specimens of BM, the subgroup of small adipocytes exhibited expression of Perilipin1 but not mitochondrial membrane protein UCP-1. Combination with the unilocular lipid droplets in adipocytes indicated that small adipocytes did not play a role in the conversion to brown adipose tissue. Conclusions: We first defined a subpopulation of small adipocytes in BM and demonstrated that only these cells but not all adipocytes were related to a poor prognosis in AML patients. The morphological changes of marrow adipocytes could be helpful to judge the prognosis of leukemia and could lead to other therapeutic perspectives. Disclosures No relevant conflicts of interest to declare.

Myelodysplastic Syndrome and Gastrointestinal Carcinomas Characterize the Cancer Risk in Diamond Blackfan Anemia: A Report from the Diamond Blackfan Anemia Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 333-333 ◽  
Author(s):  
Adrianna Vlachos ◽  
Philip S Rosenberg ◽  
Jessica Kang ◽  
Eva Atsidaftos ◽  
Blanche P Alter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cancer Risk ◽  
Myelodysplastic Syndrome ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Osteogenic Sarcoma ◽  
Diamond Blackfan Anemia ◽  
Acute Myeloid

Abstract Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by red cell aplasia and congenital anomalies. In our 2012 report the predisposition to cancer was quantified for the first time by the DBA Registry of North America (DBAR), the largest established DBA patient cohort with prospective follow-up since 1991. Five years from the original analysis, this update of the cancer incidence in patients with DBA reveals additional solid tumors, in particular gastrointestinal tumors, and an alarming incidence of myelodysplastic syndrome (MDS). In this study we report the types, ages, outcomes and hazard rates in DBA patients with neoplasia enrolled in the DBAR. The patients/families and their physicians completed a detailed questionnaire. Information was verified through medical records and telephone interviews. The ratio of observed to expected (O/E) cancers was computed using SEER data, and the cumulative incidence and hazard rate of hematopoietic stem cell transplant (HSCT), acute myeloid leukemia (AML), solid tumors (ST), and MDS by age were calculated. There were 702 patients with 12,376 person-years of follow-up. Twenty-three had solid tumors, 3 had acute myeloid leukemia (AML), and 8 had MDS. The median age at diagnosis of a solid tumor for the patients who had not received a bone marrow transplant was 35 years (range, 11-63). There were 9 gastrointestinal carcinomas (7 colon, 1 gastroesophageal, and 1 esophageal), 4 osteogenic sarcoma, 2 breast cancer and 2 squamous cell carcinomas (vaginal and oral) and 9 others, with 3 patients having more than one cancer. Cancer incidence in DBA was significantly elevated with an observed-to-expected (O/E) ratio for all cancers combined of 4.75, (95% confidence interval 3.15-6.86); significant O/E ratios were 352 for MDS, 45 for colon carcinoma, excluding rectum, 42 for osteogenic sarcoma, and 29 for AML. Although the sample size is small it appears that the cancer risk by genotype correlates only with the relative incidence of that genotype in the DBAR cohort (RPS19, 7; RPL11, 2; RPL5, 2; RPL35a, 3; and RPS17, 1). By their mid-40s, 24% had received a HSCT, 23% had died, 2% had AML, and 12% had developed a ST; 61% had died or experienced a serious adverse event. The median overall survival was 51 years and the actuarial risk of MDS in the absence of any competing risks was 50% by age 30 years. Cancer risks in DBA appear to have reached those seen in dyskeratosis congenita (DC) and are still lower than in Fanconi anemia (FA). Furthermore, the type of solid tumors in DBA (gastrointestinal carcinoma and osteogenic sarcoma) vs. FA (head and neck squamous cell carcinoma) are quite different suggesting different mechanisms of carcinogenesis from nucleolar stress vs. genomic instability. Importantly the risk of MDS in DBA is elevated, as it is in FA and DC. This report also confirms the observation that there was no specific association of cancer type or frequency with genotype. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bone marrow metastasis of glioblastoma multiforme mimicking acute myeloid leukemia

2020 ◽  
Vol 2020 (6) ◽  
Author(s):  
Akihito Nagata ◽  
Yusuke Kanemasa ◽  
Miyu Kikuchi ◽  
Ryohei Otani ◽  
Ryoji Yamada ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Glioblastoma Multiforme ◽  
Myeloid Leukemia ◽  
Morphological Characteristics ◽  
Bone Marrow Aspiration ◽  
Bone Marrow Metastasis ◽  
Severe Pancytopenia ◽  
Cluster Of Differentiation ◽  
Acute Myeloid

Abstract A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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