Sustained post‐transfusion granulocyte count increments following transfusion of leukocytes obtained from donors with chronic myelogenous leukemia

Schiffer, Charles A.; Aisner, Joseph; Dutcher, Janice P.; Wiernik, Peter H.

doi:10.1002/ajh.2830150108

Cited by 36 publications

(13 citation statements)

References 33 publications

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Section: A Brief History Of the Use Of Granulocyte Transfusionmentioning

confidence: 97%

“…Because immature myeloid progenitors were obtained from CML donors, sustained levels of circulating granulocytes were commonly seen for a number of days after single transfusions owing to continued differentiation of the myeloid precursors. Interestingly, it was also shown that the leukocyte alkaline phosphatase levels were markedly increased in the granulocytes tested ex vivo after circulation in the infected host, whereas they were characteristically decreased in the CML donors [6].Although the CML transfusions were well tolerated and demonstrably of benefit, there was increasing reluctance to utilize donors with 'cancer', with a shift towards the collection of cells from normal donors. In parallel, in the early 1970s, both continuous flow (CFC) and intermittent flow centrifugation (IFC) apheresis devices were developed which utilized rouMed Mycol Downloaded from informahealthcare.com by Nanyang Technological University on 08/24/15…”

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confidence: 96%

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Granulocyte transfusion therapy 2006: The comeback kid?

Schiffer

2006

Med Mycol

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There has been an increased interest in the use of therapeutic granulocyte transfusion in recent years because premedication of donors with granulocyte colony stimulating factors produces much higher doses of granulocytes for transfusion. Other factors which influence the outcome of transfusion include the types of infection being treated, the likelihood of recipient marrow recovery and recipient alloimmunization. This review provides a historical perspective on these issues.There has been a recent renewal of interest in the use of granulocyte transfusion, largely because of the observation that premedication of donors with granulocyte colony stimulating factor (G-CSF) permits the collection of large numbers of granulocytes resulting in higher post transfusion granulocyte increments, which are sometimes sustained for a few days post transfusion [1,2]. This 'resurrection' follows a period of more than 15 years in which granulocyte transfusions were used very sparingly. In the following, some of the reasons for this fluctuation over time will be addressed. A brief history of the use of granulocyte transfusionGranulocyte transfusions were first utilized in the early 1960s in an era characterized by a high incidence of refractory infections with gram negative bacteria, due in part to the absence of effective antibiotics and the long periods of neutropenia related to the lack of effective therapies for acute leukemia [3]. In addition, technology was not available to efficiently separate granulocytes from the upper layer of red blood cells after centrifugation. In response to this problem, investigators at the National Cancer Institute studied the transfusion of leukocytes collected from patients with chronic myelogenous leukemia (CML), initially by simple centrifugation [4], and subsequently with the use of a continuous flow blood cell separator collaboratively developed by the NCI and the IBM Corporation [5].Two important principles were established by these early studies, both of which were somewhat ignored in subsequent decades. First, there was a direct relationship between the dose of leukocytes administered and the post transfusion increments with a suggestion that improved response rates were also associated with higher doses [4]. Secondly, increments were lower and the incidence of transfusion reactions was increased in recipients who were alloimmunized, as documented by the presence of leukoagglutinating antibodies. Because immature myeloid progenitors were obtained from CML donors, sustained levels of circulating granulocytes were commonly seen for a number of days after single transfusions owing to continued differentiation of the myeloid precursors. Interestingly, it was also shown that the leukocyte alkaline phosphatase levels were markedly increased in the granulocytes tested ex vivo after circulation in the infected host, whereas they were characteristically decreased in the CML donors [6].Although the CML transfusions were well tolerated and demonstrably of benefit, there was increasing reluctance to u...

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Section: A Brief History Of the Use Of Granulocyte Transfusionmentioning

confidence: 97%

mentioning

confidence: 96%

Granulocyte transfusion therapy 2006: The comeback kid?

Schiffer

2006

Med Mycol

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“…Homografts have been described in recip ients of leukocyte transfusion obtained from CML patients [15,16]. However, all of our leukocyte concentrates were irradiated with 15 Gy, which is in general considered suffi cient to prevent cell division and engraftment of a homo graft.…”

Section: Casementioning

confidence: 99%

Reemphasis on Leukocyte Transfusions: Induction of Myeloid Marrow Recovery in Critically ill Neutropenic Children with Cancer

Saarinen¹,

Hovi²,

Vilinikka³

et al. 1995

Vox Sanguinis

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Neutropenia is the major factor predisposing to sepsis in cancer patients, and its duration is important for survival. We administered leukocyte transfusions (LT) to 10 children suffering from documented life-threatening infections during profound, prolonged neutropenia. Nine had acute leukemia, and one had aplastic anemia; three were bone marrow transplant recipients. These 10 were the only patients in our unit who received LT during the past 7 years. The median leukocyte dose was 0.6x10^9/kg in total. Instead of leukapheresis products, we used pooled buffy coats from random donors, with a high relative content of lymphocytes and especially T lymphocytes. The leukocyte concentrates were irradiated with 15 Gy. In all 10 patients, we observed prompt and sustained myeloid marrow recovery following LT. Such an effect of LT has never been described before. We hypothesize that in the internal milieu of these aplastic patients the transfused leukocytes were stimulated to secrete cytokines, the result being a cascade-like phenomenon and stimulation and proliferation of the patient’s own bone marrow cells. The bone marrow-stimulating effect of LT merits further study.

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“…negligible (b0.5%) in several other large studies [44][45][46]. The fact that CML cells could engraft transiently, eradicate or prevent infection during the neutropenic period, and subsequently be rejected upon endogenous immune recovery of the host illustrates principles that underlie NEACT.…”

Section: Historical Perspectivementioning

confidence: 97%

“…In the 1960s-1980s, non-irradiated neutrophils from chronic myeloid leukemia (CML) patients were transfused to unrelated, nonalloimmunized AML patients receiving induction or re-induction chemotherapy as a means of providing transient engraftment for supportive care [42][43][44][45][46]. This strategy antedated the use of therapeutic granulocyte transfusions obtained from normal donors (because yields were higher from CML patients [47]) and antedated granulocytecolony stimulating factor (G-CSF) therapy.…”

Section: Historical Perspectivementioning

confidence: 99%