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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3123-3130
Partially Mismatched Pediatric Transplants With Allogeneic
CD34+ Blood Cells From a Related Donor
Yoshifumi Kawano,
Yoichi Takaue,
Arata Watanabe,
Osamu Takeda,
Kohji Arai,
Etsuro Itoh,
Yuhju Ohno,
Takanori Teshima,
Mine Harada,
Tsutomu Watanabe,
Yasuhiro Okamoto,
Takanori Abe,
Teruyuki Kajiume,
Takeji Matsushita,
Kazuma Ikeda,
Mikiya Endo,
Yasuhiro Kuroda,
Shigetaka Asano,
Ryuji Tanosaki,
Ken Yamaguchi,
Ping Law, and
John D. McMannis
From the Department of Pediatrics, University of Tokushima,
Tokushima; National Cancer Center Hospital, Tokyo; the Department of
Pediatrics, University of Akita, Akita; the Department of Pediatrics,
University of Hirosaki, Aomori; Kitakyushu Medical Center, Fukuoka; the
Second Department of Internal Medicine, University of Okayama, Okayama;
the Department of Pediatrics, International Medical Center of Japan,
Tokyo; the Division of Blood Transfusion, Kagawa Medical School,
Kagawa; the Department of Pediatrics, Iwate Medical University, Iwate;
the Institute of Medical Sciences, University of Tokyo, Tokyo, Japan;
University of California San Diego, Blood and Marrow Transplantation
Program, San Diego, CA; and Baxter Healthcare Corporation, Irvine, CA.
This was a phase I, multi-center study of 13 pediatric patients
(median age, 11 years) to evaluate toxicity, hematopoietic recovery,
and graft-versus-host disease (GVHD) after allogeneic transplantation
of enriched blood CD34+ cells obtained from genotypically
haploidentical but partially HLA-mismatched related donors (8 parents
and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity
was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion
of a large amount of stem cells, peripheral blood cells (PBC) were
mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 µg/kg/d for 5 days) and
collected by 2 to 5 aphereses. To both enhance engraftment and reduce
GVHD, CD34+ cells were enriched using immunomagnetic
procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp,
Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a
median of 7.7 (range, 2.2 to 14) × 106/kg of
CD34+ cells and 1.03 (0.05 to 2.09) × 105/kg CD3+ cells were infused. Using
Center-specific posttransplant supportive care and immunosuppressive
GVHD prophylaxis, two patients experienced early death; one from
veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of
11 patients showed signs of engraftment; however, subsequent rejection
was seen in 4 patients, 2 of whom had autologous recovery. Eight
patients were evaluated in the early phase of marrow recovery. The
median number of days to achieve an absolute granulocyte count of 0.5 × 109/L was 14 (range, 9 to 20) and that to
achieve a platelet count of 20 × 109/L was 17.5 (range,
12 to 23). Donor chimerism persisted in five patients until death or
current survival. All of the surviving patients with
functioning-donor-type hematopoiesis were given total body
irradiation. De novo acute GVHD (grades II and IV) was observed in two
of the eight evaluated patients. Scheduled donor lymphocyte infusion
(DLI), using the CD34 fraction, was administered to four
patients, free of de novo acute GVHD, beginning between 28 to 43 days
after transplant. Three of these patients developed acute GVHD (grades
I, II, and IV). Cytomegalovirus infection was a major infectious
complication but was successfully managed with  -globulin and
gancyclovir treatment with or without additional DLI. Five patients are
currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of
donor origin and two of autologous origin. In conclusion, our results
show that enriched blood CD34+ cells from a mismatched
haploidentical donor are a feasible alternative source of stem cells,
but do not appear to ensure engraftment. Because none of the patients
who were administered DLI survived, the therapeutic efficacy and safety
of periodic DLI, as an integrated part of such transplants, needs to be
clarified in further studies.
© 1998 by The American Society of Hematology.
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