scholarly journals Quantitative Bone Marrow MRI in Children with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 11 (2) ◽  
pp. 141-145
Author(s):  
Galina Tereshchenko ◽  
Nataliia Kriventsova ◽  
Dmitry Kupriyanov ◽  
Peter Menshchikov ◽  
Dmitry Litvinov ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Phase ◽  
Lymphoblastic Leukemia ◽  
Healthy Controls ◽  
Specific Therapy ◽  
Fat Fraction ◽  
The Mean ◽  
Bone Structures ◽  
Dependent Samples

The aim of this study was to evaluate, using MRI, the changes in bone marrow fat fraction (BMFF) of patients with acute lymphoblastic leukemia (ALL), in comparison with children without hematological disorders. Methods and Results: The cohort of the study subjects included 20 patients aged between 5 and 17 years (mean age of 11.2±3.6 years; 10 boys and 10 girls) with clinically and morphologically confirmed diagnosis of ALL All patients underwent MRI scanning in the acute phase of the disease before the start of specific therapy. Then, the study was repeated in 10 patients (mean age of 12.2±2.3 years; 8 boys and 2 girls) during treatment, according to the ALL-MB 2015 protocol for patients with primary ALL and according to the ALL-REZ-MB 2016 protocol for patients with relapsed ALL. The control group consisted of 24 healthy controls of the same age group (mean age of 12±2.8; 17 boys and 7 girls) with no prior hematologic diseases. MRI scanning was carried out using a Philips Achieva dStream 3T scanner with a 32-channel FlexCoverage abdominal receiving coil. The MRI protocol included images obtained with the mDIXON Quant technique in the coronal plane, completely covering the pelvic bones and lumbar spine. Fat fraction (FF) maps were generated automatically on the MRI console using the 7-peak fat model and were corrected for T2* effects. Regions of interest (ROI) measuring 150 mm2 were placed in the bodies of the left and right iliac bones (Ilium L, Ilium R) as well as in the L4 and L5 vertebral bodies, taking care to avoid blood vessels, cortical bones and areas that could potentially contain artifacts. In the group of healthy controls, BMFF value was 51%±11% in the bodies of the iliac bones and 32%±10% in the lumbar vertebrae. In the group of patients with the acute phase of the disease, BMFF was as low as 3.1%±2.6% in all the bone structures. In patients who had undergone chemotherapy, the mean BMFF increased up to 77%±7% in the iliac bones and up to 65%±13% in the vertebrae. Student's t-test for dependent samples revealed a statistically significant increase in the mean BMFF values in all the bone structures after chemotherapy (P<0.01). After specific therapy, BMFF was also significantly higher than under normal conditions (P<0.01). Conclusion: This study provides important diagnostic information for various phases of ALL treatment, especially in suspected cases of resistant or recurrent disease.

scholarly journals Blood component therapy, demographic and outcome feature of pediatric acute lymphoblastic leukemia

2021 ◽  
Vol 6 (2) ◽  
pp. e37-e37
Author(s):  
Mehran Noroozi ◽  
Farid Ghazizadeh ◽  
Saba Fani
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Study Data ◽  
Blood Component ◽  
Cross Sectional ◽  
Blood Component Therapy ◽  
Pediatric All ◽  
The Mean

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with an annual incidence rate of three to four cases per 100000 children. Most children with ALL frequently receive blood products including packed cells, platelets, fresh frozen plasma (FFP) and whole blood in the course of chemotherapy and these transfusions may affect ALL outcomes. Objectives: This study aimed to evaluate blood component therapy together with demographic and outcome features of pediatric ALL patients. Patients and Methods: Demographic information of 208 patients with pediatric ALL from February 2011 to August 2019 enrolled in this cross-sectional study. Data is gathered and rechecked from archive files and e-files of Motahari hospital. Results: The mean age of patients at diagnosis was 5.48±3.38 years and Pre-B ALL was the most common phenotype (94.3%). 130 Out of 208 patients were treated with the new protocol and 78 patients were treated with the BFM98 protocol. The majority of relapses were in the bone marrow. The average of received packed cell, platelet and FFP were 4.32±2.93, 5.97±7.09 and 5.29±6.6 units, respectively. The mean overall survival of patients was 3.42±2.58 years in 10 years. Conclusion: According to this study, most of the patients were 5 to 15 years old. Dominant subtype of disease was B-cell type. Most of the deaths were one to 6 years after diagnosis. The relapse rate was about 31% and most of them were in the bone marrow.

scholarly journals Outcomes in Older Adults with Acute Lymphoblastic Leukemia (ALL) Receiving Linker Protocol at a Single Center Institution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1308-1308
Author(s):  
Cindy Lynn Hickey ◽  
David Conrad ◽  
Stephen Couban
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
The Elderly ◽  
Free Text ◽  
Text Search ◽  
Free Survival ◽  
Free Text Search ◽  
The Mean

Introduction: Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer that has predominately been regarded as a pediatric disease. However, it is estimated that 16-31% of new cases occur in adult patients, with 17% of patients diagnosed being 55 years of age or older. While the clinical outcomes of childhood ALL are excellent with complete response (CR) rates of greater than 90% and overall cure rates of 80-90%, the adult population, particularly the elderly population, fair much worse with 5-year overall survival (OS) less than 15% and 5% for patients older than 60 and 70, respectively. A large part of the success of pediatric outcomes has to do with the intensive chemotherapy regimen and so several studies have addressed the role of pediatric-inspired regimens in the elderly. The superior results of these trials favor a pediatric-based approach in the adult population however it is felt that the omission of asparaginase is an important modification for older patients. The current standard of care at our institution for patients who are 50 years of age or older is the Linker protocol based on 2002 prospective cohort study by Linker et al. With an impressive CR rate of 93% and 5-year event free survival (EFS) of 52%, we sought to retrospectively determine if the benefit of this therapy outweighed its known significant toxicity. Since the original Linker study only included 8 patients over the age of 50, we felt that the favorable outcomes may be potentially overrepresented in a much older treated population. Methods : A centralized bone marrow database search was performed for all bone marrow biopsies from January 1, 2006 to June 1, 2016 using a free text search for "acute lymphoblastic leukemia" in the bone marrow report. This was cross-referenced with the pharmacy medication dispensary database using a free text search for "asparaginase". All patients who were aged 50 years or older, had a new diagnosis of ALL (B and T cell subtype included), initiated treatment with the Linker Protocol and diagnosed between January 1 2006 to June 1 2016 were included in the study. Patients were excluded if they had relapsed or refractory ALL, under the age of 50, treated with an alternative regimen or palliated. For this study, ALL was defined based on the 2016 WHO classification. Data collected included patients age, sex, comorbidities, presenting white blood cell count, CNS involvement and ALL immunophenotype and cytogenetics. Results: A total of 125 bone marrow reports and patient charts were reviewed, and 85 patients were excluded based on the above exclusion criteria. A further 21 patients were excluded because they were either treated outside of our center, charts were not available, wrongly diagnosed or outside the timeframe of the study. The remaining 19 patients were included in the study analysis with an average follow-up time of 66 months. The mean age at diagnosis was 61 (range 51-70) with a slight male predominance of 58% (11/19). 5% of patients (1/16) had CNS involvement, with 11% unknown. B-cell immunophenotype was observed in 84% (16/19) with the remaining 16% T-cell subtype (3/19). Philadelphia chromosome and MLL rearrangements were present in 26% and 11% of patients, respectively. Cytogenetics were normal in 16%(3/19), complex in 26%(5/19), demonstrated at least 1 abnormality in 26%(5/19) and unknown in 32%(6/19). Complete remission was observed in 74%(14/19) of patients with 16% undergoing allogeneic stem cell transplant. The mean OS was 57.8 months (95%CI, 30.2-85.4) with 5-year OS of 40%, Fig 1. The mean progression free survival (PFS) was 40 months (95% CI, 19.5-60.4) with 5-year PFS of 38%, Fig 2. In a subgroup analysis of patients aged 50-59 and 60-70, 5-year OS was 70% and 20%, respectively (P-value 0.092), Fig 3. Finally, 100% of patients (19/19) had documented infection during therapy, with 47%(9/19) requiring ICU admission. Conclusion: This retrospective single center study showed that the use of an intensified pediatric-inspired regimen including asparaginase in older patients with ALL is reasonable, resulting in an impressive CR rate and 5-year OS. The benefit, however, appears to be limited to those aged 50-59 while those over 60 years of age have dismal survival rates as reported in previous literature. Certainly, with 100% infection rates and almost half of patients requiring an ICU admission, toxicity needs to be considered and this treatment should be reserved for the fit elderly population. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Outcome of Infants with Acute Lymphoblastic Leukemia Treated with Interfant-99 Protocol

2021 ◽  
pp. 1-7
Author(s):  
Gholamreza Bahoush ◽  
Pourya Salajegheh
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Demographic Data ◽  
Age At Diagnosis ◽  
Free Survival ◽  
Flow Cytometric ◽  
Number Of Patients ◽  
The Mean

Objective: The Outcome of Infants with Acute Lymphoblastic Leukemia Treated with Interfant-99 Protocol Materials and Methods: In this retrospective analytical study, all newly diagnosed infants with ALL who were treated with Interfant-99 protocol from 2004 to 2014 in Ali-Asghar Children's Hospital in Tehran were included. Demographic data including age at diagnosis, sex, initial WBC, Hb and platelet count, flow cytometric diagnosis, cytogenetic findings, follow-up duration, and their outcome was extracted from patients' medical records. All the above data were analyzed by SPSS 23 software. Results: 11 infants with ALL (5 girls and 6 boys) were included in the study. Mean and median age at diagnosis of all enrolled patients were 7.20 (std. deviation = 1.78; range = 3.57-9.37) and 7.90 months, respectively. 5 of the 11 patients had t (4; 11) and all of them were Pro-B ALL. The mean initial WBC in patients with this translocation was significantly higher than the others (193400 vs. 49166), and this difference was statistically significant (P = 0.004) despite the small number of patients under study. None of the patients had CNS involvement or mediastinal mass at diagnosis. Three patients relapsed, two of whom had isolated CNS relapse. Finally, one of them recovered completely as chemotherapy continued, another suffered a bone marrow relapse and eventually died, and a third suffered a bone marrow relapse and died about 10 months after relapse. The median follow-up of all patients was 53.83-mo. The estimated 5-yr overall survival of patients was 68.60% ± 15.10, and their Estimated 5-yr event-free survival was 21.20%±45.70. Infection was the most common complication during treatment that was manageable. Conclusion: The Interfant-99 protocol appeared to improve the outcome of infants with ALL even with t (4; 11), with manageable complications. However, its implementation in developing countries has problems due to the small number of rooms suitable for heavy chemotherapy, and the dose of drugs that should be modified. It is worth noting that proving this requires a comprehensive prospective study with an appropriate sample size.

scholarly journals Colony formation in vitro by leukemic cells in acute lymphoblastic leukemia (ALL)

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 712-718 ◽  
Author(s):  
SD Smith ◽  
EM Uyeki ◽  
JT Lowman
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Cells ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Assay System ◽  
Leukemic Cells ◽  
Specific Cell ◽  
Specific Cell Surface

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.

scholarly journals Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie L. Rellick ◽  
Gangqing Hu ◽  
Debra Piktel ◽  
Karen H. Martin ◽  
Werner J. Geldenhuys ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tumor Cells ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adherent Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.

scholarly journals Low molecular weight B-cell growth factor and recombinant interleukin-2 are together able to generate cytotoxic T lymphocytes with LAK activity from the bone marrow cells of children with acute lymphoblastic leukemia

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1355-1359 ◽  
Author(s):  
MX Zhou ◽  
HW Jr Findley ◽  
AH Ragab
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Growth Factor ◽  
Cytotoxic T Lymphocytes ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Recombinant Interleukin 2 ◽  
B Cell Growth Factor ◽  
Lak Activity

Abstract We are reporting here that low-mol wt B-cell growth factor (LMW-BCGF) and recombinant interleukin-2 (rIL-2) are together able to induce CD3+ cytotoxic T lymphocytes (CTL) with lymphokine-activated killer cell (LAK) activity from the bone marrow (BM) cells of children with acute lymphoblastic leukemia (ALL). Ficoll-Hypaque (FH)-separated BM cells were obtained from patients with active disease (at diagnosis N = 13, in relapse N = 15) and in complete remission (CR; N = 12). CD3+ cells were removed by Leu-4 antibody and immunobeads. Cells were cultured (10(5) cells/mL) in semisolid media with rIL-2 (100 mu/mL), LMW-BCGF (0.1 mu/mL), and the combination of rIL-2 plus LMW-BCGF, respectively, for seven to ten days. Pooled colonies were harvested for phenotyping. LMW-BCGF plus rIL-2 induced large numbers of CD3+ colonies from CD3- precursors. rIL-2 alone did not induce colony formation. In addition, cells were cultured in liquid media with LMW-BCGF, rIL-2, and the combination of LMW-BCGF plus rIL-2, respectively, for seven to 21 days. They were harvested for phenotyping, and cytotoxicity assays were performed v K562, Raji, and autologous leukemic cells. LMW-BCGF plus rIL-2 induced significant expansion of CD3+ cells from CD3- precursors, and these cells were activated to kill autologous leukemic cells in addition to Raji and K562 cell lines. LMW-BCGF or rIL-2 alone did not induce significant expansion or activation of cytotoxic CD3- cells. Our hypothesis is that LMW-BCGF plus rIL-2 stimulates the proliferation and activation of CD3- precursors from the BM cells of children with acute leukemia to become CD3+ cells that have LAK activity. This finding may have therapeutic implications.

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

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