cells is not present late after harvest while mild monocytopenia of unclear clinical significance may occur. Jan Storek, Monja A. Dawson, and David G. Maloney.
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cannot exclude that our donors’ lymphocyte subset counts returned to normal before 1 year after harvest. Our data suggest that quantitative deficiency of B, T, and NK cells is not present late after harvest while mild monocytopenia of unclear clinical significance may occur. Jan Storek, Monja A. Dawson, and David G. Maloney Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
Supported by National Institutes of Health (USA) grants no. CA68496 and AI46108.
References 1. Anderlini P, Korbling M, Dale D, et al. Allogeneic blood stem cell transplantation: considerations for donors [editorial]. Blood. 1997;90:903-908.
5. Storek J, Witherspoon RP, Maloney DG, Chauncey TR, Storb R. Improved reconstitution of CD4 T cells and B cells but worsened reconstitution of serum IgG levels after allogeneic transplantation of blood stem cells instead of marrow [letter]. Blood. 1997;89:3891-3893. 6. Sakamaki S, Matsunaga T, Hirayama Y, Kuga T, Niitsu Y. Haematological study of healthy volunteers 5 years after G-CSF [letter]. Lancet. 1995;346:14321433. 7. Stroncek DF, Clay ME, Herr G, Smith J, Ilstrup S, McCullough J. Blood counts in healthy donors 1 year after the collection of granulocyte-colony-stimulating factor-mobilized progenitor cells and the results of a second mobilization and collection. Transfusion. 1997;37:304-308. 8. Storek J, Ferrara S, Ku N, Giorgi JV, Champlin RE, Saxon A. B cell reconstitution after human bone marrow transplantation: recapitulation of ontogeny? Bone Marrow Transplant. 1993;12:387-398. 9. Storek J, Dawson MA, Maloney DG. Comparison of two flow cytometric methods enumerating CD4 T cells and CD8 T cells. Cytometry. 1998;33:76-82. 10. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690-695.
2. Martinez C, Urbano-Ispizua A, Rozman C, et al. Effects of G-CSF administration and peripheral blood progenitor cell collection in 20 healthy donors. Ann Hematol. 1996;72:269-272.
11. Mackall CL, Fleisher TA, Brown MR, et al. Age, thymopoiesis, and CD41 T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995; 332:143-149.
3. Korbling M, Anderlini P, Durett A, et al. Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD341 and CD341 Thy-1dim CD38progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation. Bone Marrow Transplant. 1996;18:1073-1079.
12. Okumura M, Fujii Y, Inada K, Nakahara K, Matsuda H. Both CD45RA1 and CD45RA- subpopulations of CD81 T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells. J Immunol. 1993;150:429-437.
4. Mills KC, Gross TG, Varney ML, et al. Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood. Bone Marrow Transplant. 1996;18:53-61.
13. Okumura M, Fujii Y, Takeuchi Y, Inada K, Nakahara K, Matsuda H. Age-related accumulation of LFA-1high cells in a CD81CD45RAhigh T cell population. Eur J Immunol. 1993;23:1057-1063.
To the editor: Donor lymphocyte infusions for CML: possible effects of age and mobilization We read with great interest the article on comparison of single-dose and escalating dose regimens of donor lymphocyte infusions for relapse after allografting for chronic myeloid leukemia.1 The observation that graft-versus-host disease can be minimized by staggering lymphocyte infusions, even with a similar final number of cells, is of extreme importance. Two important aspects of the methodology however are missing. The first is age of the patients and whether age is balanced equally in the 2 groups. Since younger patients have a better prognosis for overall survival and a lower rate of graft-versus-host disease following allogeneic bone marrow transplantation, this information is critical. Another important aspect of the methodology that should be clarified is whether donors received mobilization therapy or not. Since the bulk dose regimen was done during an earlier time period (August 1990 through November 1995) than the escalating dose regimen (December 1995 through January 1998), it is possible but not stated that preparation of the donor may have varied. In many centers including our own, early protocols involved donor lymphocyte infusions obtained without special preparation of the donor. These early studies were associated with a high incidence of graft-versus-host disease and pancytopenia. Subsequently, in our center and others, donor lymphocyte infusions have been obtained using cells mobilized with G-CSF or with other regimens.2-4 We2 and others3,4 have found that use of G-CSF mobilized harvests contain a large number of lymphocytes, at least equal to those of lymphocyte harvests alone. Mobilization with G-CSF, however, results in other benefits that may improve overall efficacy. First, G-CSF mobilization recruits stem cells that can help to avoid pancytopenia, one of the most common and severe complications of donor lymphocyte infusions when used alone. Second, G-CSF mobilization recruits additional effector cells (cytokine producing cells, antigen presenting cells, and others) transferred with the
T-lymphocytes, which could possibly further improve the antileukemia effect. Third, G-CSF polarizes lymphocytes from Th1 to Th2 phenotype, resulting in less cytokine reaction and less graft-versushost disease.5 Finally, G-CSF mobilization may maintain graftversus-leukemia effect while preventing graft-versus-host disease through a perforin-dependent pathway, a particularly attractive way to use donor cells. Whether these theoretical benefits of G-CSF mobilization are achievable on a practical level is not yet clear as only small studies have been reported,3,4 and results have varied from favorable3 to equivocal.4 Clarification of these points will help in the interpretation of the study and could provide important information for subsequent studies. Vijay Reddy, Jan Moreb, and Paulette Mehta Pediatric Hematology-Oncology & BMT University of Florida College of Medicine Gainesville, Florida
References 1.
Dazzi F, Szydio RM, Craddock C, et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood. 2000;95:67-71.
2.
Mehta P, Mageed A, Roberts C, et al. Donor lymphocyte infusions after bone marrow transplantation in children: series from a single institution and review of the literature. International J Pediatric Hematol Oncol. 2000; in press.
3.
Siegert W, Beyer J, Kingreen D, et al. Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSFG mobilized peripheral blood stem cell preparation. Bone Marrow Transplantation. 1998;22:579-583.
4.
Mandanas RA, Saez RA, Selby GB, et al. G-CSF mobilized donor leukocyte infusions as immunotherapy in acute leukemia relapsing after allogeneic marrow transplantation. J Hematother. 1998;7:449-456.
5.
Ferrara JL. The cytokine modulation of acute graft-versus-host disease. Bone Marrow Transplantation. 1998;21, suppl 3:S13-S51.
6.
Pan L, Teshima T, Hill GR, et al. Granulocyte colony-stimulating factormobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versushost disease. Blood. 1999;93:4071-4078.
