scholarly journals Hematologic indices in individuals with pathogenic germline DICER1 variants

2021 ◽  
Vol 5 (1) ◽  
pp. 216-223
Author(s):  
Lauren M. Vasta ◽  
Nicholas E. Khan ◽  
Cecilia P. Higgs ◽  
Laura A. Harney ◽  
Ann G. Carr ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Clinical Laboratory ◽  
Pleuropulmonary Blastoma ◽  
Laboratory Studies ◽  
Secondary Leukemia ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Clinical Center ◽  
White Blood Cell Counts ◽  
Routine Clinical Laboratory

Abstract Pathogenic germline variants in DICER1 underlie an autosomal dominant, pleiotropic tumor-predisposition disorder. Murine models with the loss of DICER1 in hematopoietic stem cell progenitors demonstrate hematologic aberrations that include reductions in red and white blood cell counts, hemoglobin volume, and impaired maturation resulting in dysplasia. We investigated whether hematologic abnormalities such as those observed in DICER1-deficient mice were observed in humans with a pathogenic germline variant in DICER1. A natural history study of individuals with germline pathogenic DICER1 variants and family controls conducted through the National Cancer Institute (NCI) evaluated enrollees at the National Institutes of Health Clinical Center during a comprehensive clinical outpatient visit that included collecting routine clinical laboratory studies. These were compared against normative laboratory values and compared between the DICER1 carriers and controls. There were no statistical differences in routine clinical hematology laboratory studies observed in DICER1 carriers and family controls. A review of the medical history of DICER1 carriers showed that none of the individuals in the NCI cohort developed myelodysplastic syndrome or leukemia. Query of the International Pleuropulmonary Blastoma/DICER1 Registry revealed 1 DICER1 carrier who developed a secondary leukemia after treatment of pleuropulmonary blastoma. We found limited evidence that the hematologic abnormalities observed in murine DICER1 models developed in our cohort of DICER1 carriers. In addition, no cases of myelodysplastic syndrome were observed in either the NCI cohort or the International Pleuropulmonary Blastoma/DICER1 Registry; 1 case of presumed secondary leukemia was reported. Abnormalities in hematologic indices should not be solely attributed to DICER1. This trial was registered at www.clinicaltrials.gov as #NCT01247597.

scholarly journals Effects of Radiation on The Capacity of The Stem Cell Compartment to Differentiate into Granulocytic and Erythrocytic Progeny

Blood ◽  
1969 ◽  
Vol 34 (2) ◽  
pp. 141-156 ◽  
Author(s):  
SAMUEL HELLMAN ◽  
HELEN E. GRATE ◽  
JOHN T. CHAFFEY
Keyword(s):  
Stem Cell ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Cell Counts ◽  
Stem Cell Compartment ◽  
Cell Pool ◽  
White Blood Cell Counts ◽  
Effects Of Radiation ◽  
Stem Cell Pool

Abstract Different methods have been used to measure the survival following radiation of the hematopoietic stem cell pool. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both methods, irradiated recipient mice receive syngeneic bone marrow. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly-formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. This latter is a granulocyte response and has been shown to be a measure of the marrow granulocyte reserve. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive initially than as measured by its ability to produce granulocytic progeny. Erythropoietic repopulating ability begins recovery more promptly than the granulopoietic. These effects appear to be due to the host milieu rather than any direct effect of radiation on the stem cells, resulting in initial conservation of granulopoiesis relative to erythropoiesis with subsequent compensatory recovery of erythropoiesis. Because of recent evidence suggesting a common stem cell, these results are interpreted as consistent with the notion that radiation affects not only stem cell proliferation, but also the direction and extent of differentiation.

Allogeneic immunotherapy by hematopoietic stem cell transplantation (ASCT) after reduced intensity conditioning (RIC) following high-dose chemotherapy for patients with acute myeloblastic leukemia (AML) in first complete remission (CR1): Reduced toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7098-7098
Author(s):  
D. Blaise ◽  
R. Tabrizi ◽  
C. Faucher ◽  
M. Mohty ◽  
J. Bay ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Probability Estimates ◽  
White Blood Cell Counts ◽  
Reduced Toxicity

7098 Background: RIC-based ASCT can be used after intensive chemotherapy in pts with CR1AML(Blaise, Cancer, 2005). Initial disease control was high and was not related to selection bias (Mohty, Leukemia, 2005).Here, we investigated if this control was maintained after a long follow-up. Methods: 37 pts (age: 51 (26–60)) with high risk clinical characteristics (70%) (Age = 50 (N=22, 59%); severe comorbidity (30%)) and/or poor risk leukemic features (65%) (Cytogenetics (35%); 2 induction courses (27%); secondary leukemia (11%), High white blood cell counts(14%) or partial remission (3%)) were treated. After CR1, pts received at least either 1 course of high dose cytarabine (24 g/m2) and anthracycline (HIDAC: N=21) or HIDAC + 1 course of. melphalan (140 mg/m2) (HDMEL) with auto-SCT Pts (HIDAC +HDM N=16). All pts were then scheduled to receive ASCT prepared with RIC (fludarabine (180 mg/m2), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (28%) or PBSC (72%). Results: With a Median follow-up of 3 years (16–70 mths). 15 pts experienced aGVHD (grade 2–4 aGVHD cumulative incidence (CI):22% (9–35). 10 and 14 pts presented a limited and extensive cGVHD respectively (CI cGVHD:65 % (50–80). 3 deaths were attributed to non-relapse causes (NRD) (AGVHD: 1; CGVHD: 2° (NRD CI: 8% (0–17). In all, 9 pts relapsed at 5 mths (2–19) (24% (9–35). Relapse was associated with the absence of cGVHD (cGVHD: 8 (0–19), no cGVHD 44% (12–76), p=.05). 25 pts are still alive in CR1 for overall survival and leukemia-free survival (LFS) probability estimates at 4 years of 65 % (48–79%) and 66% (49–80%) respectively. When restricting the analysis to the 33 pts evaluable for cGVHD, cGVHD remained the only independent risk factor positively influencing LFS (cGVHD: 81% (59–92); no cGVHD (56% (27–81), p=.05) Conclusions: We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offers a relatively low NRD while exerting a sustained leukemia control even in high risk pts deserving prospective evaluation against standard strategy of conventional Allo SCT. No significant financial relationships to disclose.

scholarly journals Effect of Cyclophosphamide on the Murine Hematopoietic Stem Cell Compartment as Measured by Different Assay Techniques

Blood ◽  
1971 ◽  
Vol 38 (6) ◽  
pp. 706-714 ◽  
Author(s):  
SAMUEL HELLMAN ◽  
HELEN E. GRATE
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Erythroid Differentiation ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Cell Pool ◽  
Murine Hematopoietic Stem Cell ◽  
White Blood Cell Counts ◽  
Stem Cell Pool

Abstract Three different methods have been used to measure the survival of the hematopoietic stem cell pool following treatment with cyclophosphamide. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both these methods irradiated recipient mice receive syngeneic bone marrow from either normal or cyclophosphamide-treated animals. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive than as measured by its ability to produce granulocytic progeny. The spleen colony assay gives results similar to the assay of granulocytic progeny. These results, taken with previous data indicating decrease in erythroid precursors in spleen colonies derived from cells surviving cyclophosphamide, are interpreted as indicating a decrease in ability for erythroid differentiation in cells surviving cyclophosphamide.

scholarly journals Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase

2020 ◽  
Author(s):  
Yuhan Xing ◽  
Wei Ni ◽  
Qin Wu ◽  
Wenjie Li ◽  
Guoju Li ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Clinical Laboratory ◽  
Fecal Excretion ◽  
Rt Pcr ◽  
Fecal Shedding ◽  
Predominant Symptom ◽  
Cell Counts ◽  
Normal White Blood Cell ◽  
Treatment Data ◽  
White Blood Cell Counts

AbstractBackgroundSevere acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Presence of SARS-CoV-2 has been constantly reported in stools of patients with coronavirus disease 2019 (COVID-19). However, there is a paucity of data concerning fecal shedding of the virus in pediatric patients.ObjectiveTo investigate dynamic changes of SARS-CoV-2 in respiratory and fecal specimens in children with COVID-19.MethodsFrom January 17, 2020 to February 23, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Patients were followed up to March 10, 2020, the final date of follow-up, and dynamic profiles of RT-PCR results were closely monitored.ResultsAll the three pediatric cases were household contacts of adults whose symptoms developed earlier. Severity of disease was mild to moderate and fever was the most consistent and predominant symptom at onset of illness of these children (two cases had body temperature higher than 38.5°C). All children showed increased lymphocytes (>4.4×109 /L) with normal white blood cell counts on admission. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained positive in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 turned negative 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.InterpretationSARS-CoV-2 may exist in gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

scholarly journals BCR-ABL expression in different subpopulations of functionally characterized Ph+ CD34+ cells from patients with chronic myeloid leukemia

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1796-1804 ◽  
Author(s):  
V Maguer-Satta ◽  
AL Petzer ◽  
AC Eaves ◽  
CJ Eaves
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Very High Frequency ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Actin Mrna ◽  
White Blood Cell Counts

Abstract In patients with chronic myeloid leukemia (CML), the leukemic (BCR- ABL+/Ph+) clone typically includes cells belonging to all of the myeloid lineages and frequently some B cells. From such observations it has been inferred that the initial BCR-ABL gene rearrangement event occurs in a pluripotent hematopoietic stem cell and that the clone subsequently generated is maintained by a subpopulation of neoplastic, BCR-ABL-expressing cells that retain at least some of the defining properties of normal hematopoietic stem cells. To test this hypothesis directly, we isolated various subpopulations of CD34+ cells from fresh or cryopreserved samples of peripheral blood from 5 CML patients with high white blood cell counts, 4 of which were selected because of their exclusive content of Ph+ progenitors (both colony-forming cells and long-term culture-initiating cells [LTC-IC]). Cells in each of the CD34+ subpopulations isolated were examined for the presence of BCR-ABL mRNA using a reverse transcriptase-polymerase chain reaction technique that reproducibly gave a positive signal from single K562 cells. BCR- ABL mRNA was detected in 117 of 147 samples (80%) in which actin mRNA was demonstrable. This included 60% to 90% of a large number of individually analyzed CD34+ cells including 46 single CD34+CD71-CD38- cells and 27 single CD34+CD71+CD38+ cells from 3 patients. In 2 of these cases, the same populations also contained a very high frequency of Ph+ LTC-IC. Our findings demonstrate BCR-ABL gene expression in neoplastic cells with functional as well as surface marker characteristics of very primitive normal hematopoietic cells. This implicates the BCR-ABL gene product directly in the acquisition by these cells of properties that alter their interactions with the microenvironment and deregulate their proliferation control.

scholarly journals BCR-ABL expression in different subpopulations of functionally characterized Ph+ CD34+ cells from patients with chronic myeloid leukemia

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1796-1804 ◽  
Author(s):  
V Maguer-Satta ◽  
AL Petzer ◽  
AC Eaves ◽  
CJ Eaves
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Very High Frequency ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Actin Mrna ◽  
White Blood Cell Counts

In patients with chronic myeloid leukemia (CML), the leukemic (BCR- ABL+/Ph+) clone typically includes cells belonging to all of the myeloid lineages and frequently some B cells. From such observations it has been inferred that the initial BCR-ABL gene rearrangement event occurs in a pluripotent hematopoietic stem cell and that the clone subsequently generated is maintained by a subpopulation of neoplastic, BCR-ABL-expressing cells that retain at least some of the defining properties of normal hematopoietic stem cells. To test this hypothesis directly, we isolated various subpopulations of CD34+ cells from fresh or cryopreserved samples of peripheral blood from 5 CML patients with high white blood cell counts, 4 of which were selected because of their exclusive content of Ph+ progenitors (both colony-forming cells and long-term culture-initiating cells [LTC-IC]). Cells in each of the CD34+ subpopulations isolated were examined for the presence of BCR-ABL mRNA using a reverse transcriptase-polymerase chain reaction technique that reproducibly gave a positive signal from single K562 cells. BCR- ABL mRNA was detected in 117 of 147 samples (80%) in which actin mRNA was demonstrable. This included 60% to 90% of a large number of individually analyzed CD34+ cells including 46 single CD34+CD71-CD38- cells and 27 single CD34+CD71+CD38+ cells from 3 patients. In 2 of these cases, the same populations also contained a very high frequency of Ph+ LTC-IC. Our findings demonstrate BCR-ABL gene expression in neoplastic cells with functional as well as surface marker characteristics of very primitive normal hematopoietic cells. This implicates the BCR-ABL gene product directly in the acquisition by these cells of properties that alter their interactions with the microenvironment and deregulate their proliferation control.

An Alternative Elastase-mediated Degradation of Fibrinogen and Fibrin Observed in a Patient with Herpes Simplex Encephalitis and Pneumonia

1996 ◽  
Vol 76 (02) ◽  
pp. 184-186 ◽  
Author(s):  
Kenji lijima ◽  
Fumiyo Murakami ◽  
Yasushi Horie ◽  
Katsumi Nakamura ◽  
Shiro Ikawa ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Blood Cell ◽  
White Blood Cell ◽  
Herpes Simplex Encephalitis ◽  
Pmn Elastase ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Sds Page ◽  
White Blood Cell Counts ◽  
Pmn Élastase

SummaryA 74-year-old female developed pneumonia following herpes simplex encephalitis. Her white blood cell counts reached 28,400/μl, about 90% of which consisted of granulocytes. The polymorphonuclear (PMN) elastase/α1-arantitrypsin complex levels increased and reached the maximum of 5,019 ng/ml, indicating the release of a large amount of elastase derived from the granulocytes. The mechanism of PMN elastase release was most likely to be granulocyte destruction associated with phagocytosis. The cleavage of fibrinogen and fibrin by PMN elastase, independent of plasmin, was indicated by the presence of the fragments in immunoprecipitated plasma from the patient corresponding to elastase-induced FDP D and DD fragments and the absence of fragments corresponding to plasmin-induced FDP D and DD fragments on SDS-PAGE. These findings suggested that the large amount of PMN elastase released from the excessive numbers of granulocytes in this patient with herpes simplex encephalitis and pneumonia, induced the cleavage of fibrinogen and fibrin without the participation of plasmin.

A Hexagonal (II) Phase Phospholipid Neutralization Assay for Lupus Anticoagulant Identification

1993 ◽  
Vol 70 (05) ◽  
pp. 787-793 ◽  
Author(s):  
Douglas A Triplett ◽  
Linda K Barna ◽  
Gail A Unger
Keyword(s):  
Hemophilia A ◽  
Clinical Laboratory ◽  
Neutralization Assay ◽  
Confirmatory Test ◽  
Specific Factor ◽  
Clinical Settings ◽  
Drug Induced ◽  
Variable Screening ◽  
Routine Clinical Laboratory

SummaryLupus anticoagulants (LAs) are immunoglobulins (IgG, IgM, or both) which interfere with in vitro phospholipid (PL) dependent tests of coagulation (e.g. APTT, dilute PT, dilute Russell Viper Venom Time). These antibodies may be identified in a wide variety of clinical settings. With the exception of heparinized patient samples, the presence of LAs is often the most common cause of an unexplained APTT in a routine clinical laboratory. The diagnosis of LAs is difficult due to variable screening reagent sensitivity and intrinsic heterogeneity of LAs. Recently, Rauch and colleagues have shown human monoclonal hybridoma LAs were inhibited by hexagonal (II) phase PLs. In contrast, lamellar phase PLs had no effect. We have evaluated a new assay system, Staclot LA®, which utilizes a hexagonal (II) phase PL (egg phosphatidylethanolamine [EPE]) as a confirmatory test for LAs. Plasma samples from the following patient populations were studied: LA positive, heparinized, oral anticoagulated, hemophilia A and B, and specific factor inhibitors (factors V, VIII, IX). Unlike previous studies, the LA positive patients were a mixed population including: autoimmune diseases, drug-induced, and post-infection. Our findings confirm the specificity of hexagonal (II) phase PL neutralization of LAs.

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