Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation.
OBJECTIVE
Insufficient production of leukocytes, thrombocytes and erythrocytes after allogeneic peripheral blood stem cell transplantation (PBSCT) represents a life-threatening complication.


METHODS
In 20 adult patients with poor graft function (PGF defined as transfusion-dependent platelet counts <20,000/µl, or leukocytes <1500/µl, or transfusion-dependent anemia) and variable causes of PGF after allogeneic PBSCT, immunomagnetically selected CD34(+) stem cell boosts (SCB) from matched unrelated (n = 8), mismatched unrelated (n = 11) or haploidentical (n = 1) donors were applied without prior conditioning.


RESULTS
Patients received a median of 4.6 × 10(6) CD34(+) cells per kilogram bodyweight (1.9-9.1 × 10(6)) and low T cell numbers (median 0.2 × 10(4), range 0.04-0.6 × 10(4)). All patients showed responses in at least one hematopoietic lineage. Engraftment for platelets, leukocytes and hemoglobin was 88, 88 and 100 % after a median of 14, 13 and 18 days, respectively. With regard to the complete cohort, 90 % (n = 18) showed an increase in platelets (median 76,500/µl, range -7000 to 223,000/µl), 95 % (n = 19) had an increase in leukocytes (median 3110/µl, range 150-13,740/µl) and 90 % (n = 18) improved with regard to hemoglobin (median 1.9 g/dl, range -0.9 to 5.1 g/dl). Due to effective T cell depletion, only one patient developed graft versus host disease (GvHD, grade III) after SCB. Patients were followed for a median of 7.5 months (1-74 months) with 11 patients being alive and disease free with normalized peripheral blood counts at the end of follow-up.


CONCLUSIONS
CD34(+)-selected SCB are safe and effective and can durably improve PGF even in patients receiving grafts from unrelated matched or mismatched donors with low incidence of GvHD.
Abteilung II für Onkologie, Hämatologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Otfried Müller Str. 10, 72076, Tübingen, Germany. sebastian.haen@med.uni-tuebingen.de.|Abteilung Immunologie, Interfakultäres Institut für Zellbiologie, Auf der Morgenstelle 15, 72076, Tübingen, Germany. sebastian.haen@med.uni-tuebingen.de.
Sebastian P
SP
Haen
Klinik für Kinder- und Jugendmedizin, Hoppe Seyler Str. 1, 72076, Tübingen, Germany.
Michael
M
Schumm
Abteilung II für Onkologie, Hämatologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Otfried Müller Str. 10, 72076, Tübingen, Germany.
Christoph
C
Faul
Abteilung II für Onkologie, Hämatologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Otfried Müller Str. 10, 72076, Tübingen, Germany.
Lothar
L
Kanz
Abteilung II für Onkologie, Hämatologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Otfried Müller Str. 10, 72076, Tübingen, Germany.
Wolfgang A
WA
Bethge
Abteilung II für Onkologie, Hämatologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Otfried Müller Str. 10, 72076, Tübingen, Germany.
Wichard
W
Vogel
D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011379:Prognosis; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
D018952:Antigens, CD34
Allogeneic hematopoietic cell transplantation; CD34+-selected stem cell boost; Graft versus host disease; Poor graft function