Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. II. Enhanced recovery of megakaryocytes and platelets

Abstract Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.

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Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. II. Enhanced recovery of megakaryocytes and platelets

Blood ◽

10.1182/blood.v56.1.58.bloodjournal56158 ◽

1980 ◽

Vol 56 (1) ◽

pp. 58-63 ◽

Cited By ~ 1

Author(s):

PJ Smith ◽

CW Jackson ◽

MA Whidden ◽

CC Edwards

Keyword(s):

Bone Marrow ◽

Enhanced Recovery ◽

Rapid Recovery ◽

Whole Body ◽

Platelet Recovery ◽

Clinical Advantage ◽

Rate Of Recovery ◽

Bone Marrow Regeneration ◽

Regenerative Phase ◽

Striking Effect

Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.

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Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. enhanced granulopoietic recovery

Blood ◽

10.1182/blood.v56.1.52.52 ◽

1980 ◽

Vol 56 (1) ◽

pp. 52-57 ◽

Cited By ~ 8

Author(s):

PJ Smith ◽

CW Jackson ◽

LW Dow ◽

CC Edwards ◽

MA Whidden

Keyword(s):

Bone Marrow ◽

Whole Body ◽

Rate Of Recovery ◽

Total Bone Marrow ◽

Blood Granulocyte ◽

Bone Marrow Regeneration ◽

And Control ◽

Marrow Cellularity ◽

Regenerative Phase ◽

Sublethal Irradiation

Abstract Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.

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Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. enhanced granulopoietic recovery

Blood ◽

10.1182/blood.v56.1.52.bloodjournal56152 ◽

1980 ◽

Vol 56 (1) ◽

pp. 52-57

Author(s):

PJ Smith ◽

CW Jackson ◽

LW Dow ◽

CC Edwards ◽

MA Whidden

Keyword(s):

Bone Marrow ◽

Whole Body ◽

Rate Of Recovery ◽

Total Bone Marrow ◽

Blood Granulocyte ◽

Bone Marrow Regeneration ◽

And Control ◽

Marrow Cellularity ◽

Regenerative Phase ◽

Sublethal Irradiation

Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.

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Kinetics and Fate of 111Indium-Oxine Labelled Blood Platelets in Asplenic Subjects

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650093 ◽

1980 ◽

Vol 44 (02) ◽

pp. 100-104 ◽

Cited By ~ 11

Author(s):

Anthon duP Heyns ◽

Matthys G Lötter ◽

Philip N Badenhorst ◽

Otto van Reenen ◽

Henry Pieters ◽

...

Keyword(s):

Bone Marrow ◽

Blood Platelets ◽

Normal Subjects ◽

Lower Limbs ◽

Whole Body ◽

Computer Assisted ◽

Scintillation Camera ◽

Survival Curves ◽

Platelet Recovery ◽

Body Activity

SummaryThe survival, tissue distribution and fate of 111Indium-oxine labelled autologous platelets was studied in four asplenic subjects with serial blood sampling, scintillation camera and computer-assisted imaging. Mean 111In-platelet recovery in the circulation was 89 ± 13% (± 1 SD). Platelet survival curves fitted a linear function best and was 238 ± 41 h. The shape of the survival curves of normal and asplenic subjects differed: in the asplenic subjects the curve was linear whereas that of normal subjects was significantly more curvilinear if analyzed by least squares computer fitting to a gamma function. Early hepatic 111In-activity was significant and transient and ascribed to the "collection injury". As labelled platelets disappeared from the circulation, 111Inactivity in the liver increased progressively and linearly to reach 42.5 ± 14.1 % of whole body activity at 240 h. Radioactivity also accumulated in the bone marrow, but could not be demonstrated in the vasculature of the lower limbs. These results would indicate that in asplenic subjects the major sites of destruction of senescent platelets are the liver and bone marrow.

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Megakaryocyte growth and development factor stimulates enhanced platelet recovery in mice after bone marrow transplantation

Blood ◽

10.1182/blood.v88.4.1509.bloodjournal8841509 ◽

1996 ◽

Vol 88 (4) ◽

pp. 1509-1514 ◽

Cited By ~ 35

Author(s):

G Molineux ◽

CA Hartley ◽

P McElroy ◽

C McCrea ◽

IK McNiece

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Blood Cell ◽

Marrow Transplantation ◽

Growth And Development ◽

Enhanced Recovery ◽

Cell Surface Receptor ◽

Platelet Recovery ◽

Development Factor ◽

Surface Receptor

Megakaryocyte growth and development factor (MGDF) is a recently characterized ligand for the cell surface receptor mpl. We have evaluated the effects of polyethylene glycollated recombinant human MGDF (PEG-rHuMGDF) on recovery of hematopoietic cells in mice following bone marrow transplantation (BMT) to support lethal irradiation. Mice treated with PEG-rHuMGDF (50 micrograms/kg/d) had accelerated recovery of platelet numbers compared with BMT mice treated with carrier or recombinant human granulocyte colony-stimulating factor (rHuG-CSF, 72 or 200 micrograms/kg/d). In contrast, PEG-rHuMGDF had no effect on white blood cell (WBC) or red blood cell (RBC) recovery. As previously reported, animals treated with rHuG-CSF had an enhanced recovery of WBC but not platelet or RBC levels. Interestingly, BMT receipient mice treated with the combination of PEG-rHuMGDF and rHuG-CSF showed simultaneous enhanced recovery of both leukocytes and platelets. PEGylated rHuMGDF was found to be considerably more potent than non- PEGylated rHuMGDF in this setting. PEG-rHuMGDF is an effective growth factor for enhancing platelet recovery in mice following BMT either alone or in combination with rHuG-CSF. It will be of interest to evaluate in a clinical setting the ratios of PEG-rHuMGDF and rHuG-CSF for simultaneous administration of these factors and accelerated recovery of both leukocytes and platelets.

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Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.9.1609 ◽

1991 ◽

Vol 9 (9) ◽

pp. 1609-1617 ◽

Cited By ~ 15

Author(s):

S D Huan ◽

J C Yau ◽

F R Dunphy ◽

R O Wallerstein ◽

K Dicke ◽

...

Keyword(s):

Bone Marrow ◽

Solid Tumors ◽

Enhanced Recovery ◽

Autologous Bone Marrow ◽

High Dose ◽

Platelet Recovery ◽

Hematopoietic Recovery ◽

Autologous Bone ◽

Marrow Infusion ◽

The Impact

Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients.

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HEMOPOIETIC COLONY STUDIES

Journal of Experimental Medicine ◽

10.1084/jem.127.1.205 ◽

1968 ◽

Vol 127 (1) ◽

pp. 205-214 ◽

Cited By ~ 212

Author(s):

N. S. Wolf ◽

J. J. Trentin

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Whole Body ◽

Marrow Cavity ◽

Normal Spleen ◽

Colony Forming Units ◽

X Irradiation ◽

Marrow Stroma ◽

Exogenous Origin ◽

Bone Marrow Regeneration

In heavily irradiated mice, bone marrow regeneration of either endogenous or exogenous origin was shown to occur in discrete foci comparable to the more intensively studied spleen colonies. The number of endogenous bone marrow colonies was inversely related to dose of whole body X-irradiation. Endogenous marrow colonies were found after higher doses of irradiation than were endogenous spleen colonies. Most of them were granulocytic in nature. Exogenous bone marrow colonies in lethally irradiated mice injected with bone marrow cells were proportional in number to the dose of cells injected, appeared at a time comparable to spleen colonies like which, at 7 or 8 days, they were of single differentiated cell line, either granuloid or erythroid or megakaryocytic, with a small percentage of "mixed" colonies. Whereas erythroid colonies outnumber granuloid colonies in spleen, either in situ or subcutaneously transplanted (E:G colony ratio of about 3.5), granuloid colonies outnumber erythroid in bone marrow (E:G colony ratio of about 0.7). The characteristic E:G colony ratios of spleen and marrow appear more likely to be the result of a hemopoietic organ stromal influence on pluripotent colony forming units (CFU's) than of selective lodgment of committed (unipotent) granuloid and erythroid CFU's in bone marrow and spleen, respectively, as indicated by the following. Bone marrow stem cells (CFU) which had reseeded the marrow cavity of irradiated primary recipients 18–24 hr earlier, were reharvested and retransplanted intravenously into irradiated secondary hosts. The E:G colony ratio of the colonies formed in the spleen of the secondary hosts was typical of primary spleen colonies (2.8), that of the colonies formed in the marrow cavity was typical of bone marrow colonies (0.6). Pieces of marrow stroma containing reseeded CPU's from the contralateral femur of these same primary recipients were implanted by trocar directly into the spleens of other irradiated secondary recipients. Those CPU's that developed in the intrasplenic-implanted marrow stroma yielded an. E:G colony ratio of 0.1. Those that migrated into the contiguous and remote portions of the spleen gave E:G colony ratios of 2.9 and 2.4, respectively. Irradiated marrow stroma and normal spleen CPU's (a 1 mm cube of spleen) were loaded into the same trocar and implanted directly into the spleens of irradiated mice. The spleen CFU's that migrated into the implanted marrow stroma yielded five granuloid and two mixed colonies. The larger number that developed in the host spleen yielded an E:G colony ratio of 2.9 or higher. Of those 19 mixed colonies that bridged the junction of spleen and implanted marrow stroma in each of the above two experiments, in every case, the erythroid portion of the colony was in the splenic stroma, the granuloid portion was in the marrow stroma.

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Bone Marrow Regeneration in Germfree NO-2 Mice after 700 Rad Whole Body Irradiation

Radiation Research ◽

10.2307/3573645 ◽

1972 ◽

Vol 51 (1) ◽

pp. 72 ◽

Cited By ~ 3

Author(s):

H. Heit ◽

T. M. Fliedner ◽

I. Fache

Keyword(s):

Bone Marrow ◽

Whole Body ◽

Bone Marrow Regeneration

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Clostridium haemolyticum Infection: A Cause of Hemolytic Anemia in a Patient with Bone Marrow Necrosis

Microorganisms ◽

10.3390/microorganisms9081568 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1568

Author(s):

Anne Sophie Lagneaux ◽

Sandrine Hénard ◽

Laure Diancourt ◽

Emmanuelle Stein ◽

Pierre Perez ◽

...

Keyword(s):

Bone Marrow ◽

Hemolytic Anemia ◽

Obese Woman ◽

Molecular Techniques ◽

Significant Past Medical History ◽

Bone Marrow Necrosis ◽

Rdna Sequencing ◽

Oxygen Sensitive ◽

Bacteremic Episode ◽

Bone Marrow Regeneration

Clostridium haemolyticum is a sporulating Gram-positive anaerobic rod that is considered to be one of the most fastidious and oxygen-sensitive anaerobes. It is a well-known animal pathogen and the cause of bacillary hemoglobinuria primarily in cattle. To date, human infections caused by C. haemolyticum have been reported in three patients with malignant underlying diseases. We present herein the case of a 30-year-old obese woman with no significant past medical history who developed bacteremia caused by C. haemolyticum with massive intravascular hemolysis associated with bone marrow necrosis and acute renal failure. Because of subculture failure, the diagnosis was made on the basis of 16S rDNA sequencing and next-generation sequencing. The patient, who had been afebrile for 20 days after a 17-day-course of antibiotics, experienced a second bacteremic episode caused by C. haemolyticum. After having been successfully treated for 42 days with clindamycin and amoxicillin-clavulanic acid, the patient developed acute myeloid leukemia as a result of bone marrow regeneration. Although uncommon in humans, infections caused by C. haemolyticum are severe and should be considered in a febrile patient who has severe hemolytic anemia. This case also highlights the importance of using molecular techniques for the identification of this fastidious anaerobic organism.

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