The Transfusion of Leukocytes from Donors with Chronic Myelocytic Leukemia to Patients with Leukopenia*

Abstract

Leukocytes were collected from donors with chronic myelocytic leukemia by plasmapheresis and transfused into severely leukopenic recipients. The median transfusion of 7 x 1010 granulocytes (range .15 to 35 x 1010) resulted in a median increase in circulating granulocytes of 1,000 per cu. nun.(range 0 to 19,OOO), one hour after injection. The posttransfusion increment was directly related to the number of cells injected. Only 4.8 per cent of the injected cells were recovered in the circulating blood volume at one hour (range 0-37 per cent). The per cent recovery was directly related to the pretransfusion granulocyte count of the recipient; the more severe the recipient's leukopenia, the lower w-as the per cent recovery of transfused cells. The transfused granulocytes disappeared from the recipients' circulation with a half time of 24 hours.A number of other factors were found to influence the results of transfusion, such as: the antileukemic drugs given, the presence of fever, the transfusion vehicle (k, saline concentrates or whole plasma), the ABO red cell compatibility of donor and recipient, and the sequence of transfusion.Clinical responses as measured by disappearance of fever were seen in 54 per cent of the recipients. The fraction of febrile patients responding increased as the dose of leukocytes transfused increased. Severe reactions, manifested by dyspnea, cyanosis, and lung infiltrates were seen in a small percentage, but febrile reactions occurred in 67 per cent of afebrile patients.

Neutropenia, Inflammation, and the Kinetics of Transfused Neutrophils in Rabbits

“…that the blood recovery of transfused neutrophils is related to the recipient's pretransfusion neutrophil count (7). That this may be due in part to a relative increase in marginal pool size is suggested by studies showing larger than predicted neutrophil count increments in neutropenic subjects infused with epinephrine (8).…”

“…7 and 27.6+8.8% at zero and 4 h after implantation respectively (normal, 38.2±9.9%). Transit through the CNP was hastened by inflammation with a t1/2 of 2.02±0.72 h (normal, 3.2± 1.0 h).…”

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

“…[10][11][12][13][14] Finally, many physicians were not convinced that their patients experienced meaningful clinical improvements after receiving granulocyte transfusions, which has been attributed, at least in part, to the likelihood that the doses of granulocytes administered, typically 20 to 30 3 10 9 , were inadequate. Evidence for the importance of dose came from early uncontrolled trials in humans, 15,16 from retrospective analysis of the early controlled trials, 9,17,18 from animal studies using sepsis and meningitis models, 19,20 and from human kinetic studies showing that normal daily neutrophil production in the uninfected subject was ;1 3 10 9 /kg. 21 Renewed interest in this therapy arose with the introduction of granulocyte colonystimulating factor (G-CSF) and the possibility of greatly increasing the dose of granulocytes transfused by administering G-CSF to healthy granulocyte donors.…”

Granulocyte Transfusion Therapy of Experimental Pseudomonas Pneumonia

“…The chief problem was the lack of techniques for obtaining sufficient cells from the blood of normal individuals to substantially raise the blood granulocyte counts (18). This problem led numerous investigators to study the use of patients with chronic myelogenous leukemia (CML) as leukocyte donors (19)(20)(21). Clinical trials suggested that leukocytes could reduce fever and favorably influence the course of infections in leukopenic subjects.…”

“…They were chosen because of previous experience with the effects of total body irradiation on these dogs (10) and because dogs of this size could be easily handled. The dogs used as leukocyte and platelet donors were English-American foxhounds, weighing [20][21][22][23][24][25][26][27][28][29][30] kg. These animals, entirely unrelated to beagles, were chosen as blood product donors because of their large size and docile temperament.…”