Effect of Hypertransfusion on Granulopoiesis in Bone Marrow Depression: Studies in the Irradiated Mouse

Abstract

The response of granulopoietic activity in bone marrow depression to a reduction in the demand for erythropoiesis has been examined by means of hypertransfusing C-57B mice which had been exposed to sublethal whole body irradiation. Multiple intraperitoneal injections of 0.5 ml packed red cells from irradiated donors were employed to maintain the haematocrit sufficiently above the normal range to produce significant suppression of erythropoietic activity for the duration of the bone marrow depression. This was associated with elevation above control values of 32--102% in the blood granulocyte count, 22--78% in total cells of the granulocytic series per femur, and up to 44% in total agar colony forming units per femur. Restoration of essentially normal values occurred 13 d after irradiation in contrast to 17--18 d in controls. Single transfusions which produced less suppression of erythroblast numbers per femur resulted in an intermediate degree of improvement in these parameters. Such changes in the granulocyte compartment indicate improved granulopoietic capacity in the hypertransfused group. It is suggested that this effect reflects increased production of granulocyte progenitors due to the reduction in competing demands on the compromised multipotential stem cell compartment for progenitors of the erythroid series. The findings raise the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis in human bone marrow depression.

A multicenter pilot‐randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation

“…Other potential benefits may include more rapid neutrophil and PLT recovery, improved functional status, and improved quality of life. [50][51][52][53][54][55][56][57][58][59][60][61] In addition, a high pretransplant Hb level has been demonstrated to be associated with improved survival. 62 In contrast, there is evidence that, in certain patient populations, RBC transfusion may be associated with decreased early or long-term survival.…”

“…Based on experimental animal studies, 11 we have hypothesized that this effect may be especially important in patients with thrombocytopenia including patients with AML receiving induction chemotherapy and patients undergoing SCT. Other potential benefits may include more rapid neutrophil and PLT recovery, improved functional status, and improved quality of life 50‐61 . In addition, a high pretransplant Hb level has been demonstrated to be associated with improved survival 62 .…”

Excess of Veno-Occlusive Disease in a Randomized Clinical Trial on a Higher Trigger for Red Blood Cell Transfusion after Bone Marrow Transplantation: A Canadian Blood and Marrow Transplant Group Trial

“…Studies conducted before the AIDS pandemic in children with acute lymphoblastic leukemia and in murine models have shown that maintaining high hemoglobin levels after chemotherapyinduced bone marrow depression accelerated granulocyte recovery. This accelerated recovery is related to an increase in bone marrow granulocyte progenitors, suggesting the reduced demand for erythropoiesis leaves more stem cells available for differentiation into nonerythroid cells [4][5][6][7][8]. Although granulocyte colony-stimulating factor can also be used to accelerate neutrophil recovery, it delays platelet engraftment as well as immune recovery and increases the incidence of graft-versus-host disease (GVHD), treatmentrelated mortality, and death [9][10][11][12][13][14].…”

Can hypertransfusion attenuate myelosuppression associated with combination chemotherapy in patients with inoperable bronchogenic carcinoma? A report of a randomised, controlled study

“…A different approach to this problem is to hypertransfuse red blood cell to patients prior to chemotherapy. Hypertransfusion has been shown to increase the rate of granulopoietic recovery in children receiving induction chemotherapy for acute leukemia [5,6], probably by reducing the demand for erythroid precursors and hence increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment [3,4,18]. Primary hemic malignancies, however, have a basic white cell abnormality, and interpretation of the effect of hypertransfusion would be more difficult.…”

“…It has been shown by animal experiments that pluripotent stem cells exist in mammalian bone marrow [ 1 J, and the erythroid and granulocytic pathways may compete for precursor cells arising from these stem cells. There is good experimental evidence that anemia may direct the stem cells into erythroid pathway [2], and conversely, when red cells are hypertransfused to reduce the demand for erythroid precursors, granulocytic development can be enhanced [3,4]. More recently, the role of this "stem-cell competition'' in human disease has been examined.…”