Donor Leukocyte Infusion for Leukemic Relapse After Allogeneic Marrow Transplantation: Lack of Residual Donor Hematopoiesis Predicts Aplasia

Abstract

We assessed the chimerism of CD34+ bone marrow cells before donor leukocyte infusion (DLI) on nine occasions in seven patients with leukemic relapse after allogeneic marrow transplantation. The patients suffered from acute lymphoblastic leukemia (n = 1), acute myeloid leukemia (n = 3), and chronic myeloid leukemia (CML; n = 3). Two patients received a second DLI because of disease progression after the first one. The origin of the CD34+ cells was determined by analyzing variable number of tandem repeats with polymerase chain reaction and, in sex-mismatched cases, by fluorescence in situ hybridization. Before DLI CD34+ cells were exclusively of donor origin in four patients. In another patient 41% of CD34+ cells were derived from the donor. No aplasia occurred in these patients after DLI, whereas in the two patients with exclusively recipient hematopoiesis severe aplasia lasting for 5 and 13 weeks necessitated hematopoietic stem cell support. One patient who had only 5% CD34+ donor cells before DLI recovered without stem cell support after 10 days. Two patients in relapse of CML showed a high percentage of BCR-ABL− CD34+ cells of recipient origin before DLI. These BCR-ABL− cells of recipient type did not prevent severe aplasia which indicates that the assessment of BCR-ABL+ hematopoiesis alone is insufficient for predicting aplasia. Our data indicate that in case of sufficient donor hematopoiesis before DLI no persistent aplasia will occur. Thus, evaluation of donor hematopoiesis allows prediction of aplasia after DLI and makes early therapeutic interventions possible.

Comparison of second transplantation and donor lymphocyte infusion for donor mixed chimerism after allogeneic stem cell transplantation for nonmalignant diseases

“…10 The cumulative incidence of DLI-induced cytopenia in our cohort was similar to that found after DLI for malignant diseases (18-50%) 9,10 : in those studies, a lower level of donor chimerism was recognized as a risk factor. 9,10 In the present study, acute GVHD after DLI was associated with development of cytopenia. make the important observation that DLI is a promising treatment for most patients having a higher level of donor chimerism, while second HSCT contributes to higher rates of stable engraftment and is beneficial for patients having lower levels of donor chimerism.…”

Harnessing graft‐versus‐malignancy: non‐myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy

“…Antileukaemic effectors presumably proliferate in vivo after the infusion, and presumably must reach a threshold level to eradicate the leukaemia and normal haematopoietic cells that are host derived (Hoffmann et al , 1993). Marrow aplasia may occur unless sufficient donor‐derived normal progenitors are present to restore haematopoiesis (Keil et al , 1997). Consistent with this premise, CML patients with advanced relapse more frequently develop marrow aplasia than patients treated in cytogenetic or early haematological relapse (Van Rhee et al , 1994; Keil et al , 1997).…”

“…Marrow aplasia may occur unless sufficient donor‐derived normal progenitors are present to restore haematopoiesis (Keil et al , 1997). Consistent with this premise, CML patients with advanced relapse more frequently develop marrow aplasia than patients treated in cytogenetic or early haematological relapse (Van Rhee et al , 1994; Keil et al , 1997). Patients developing aplasia generally recover after a second infusion of donor haematopoietic stem cells from either marrow or mobilized peripheral blood.…”

Prophylactic red blood cell exchange for prevention of severe immune hemolysis in minor ABO‐mismatched allogeneic peripheral blood progenitor cell transplantation after reduced‐intensity conditioning

“…In patients receiving the Seattle protocol, the numbers of days with ANC below 0.5 × 10 9 per L and PLT counts below 20 × 10 9 per L are given. For serially chimerism, analyses on Days 28, 56, 84, 180, and 360 after RIC‐HPBPCT CD3+ and CD33+ peripheral blood cells and granulocytes were isolated with flow cytometry 15 . Quantitative chimerism analysis was based on amplification of the STR loci D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D13S317, and D7S820 and the sex marker amelogenin with a PCR amplification kit as recommended by the manufacturer (AmpFlSTR Profiler, Applied Biosystems, Foster City, CA).…”