Poor graft function (PGF) can be a life-threatening post-transplantation complication for patients undergoing allogeneic hematopoietic cell transplantation (HCT). While primary graft failure has been quite rare (about 2%) in recent years, about one quarter of patients with full donor chimerism suffer from secondary graft dysfunction defined as leukocytes < 1000/μl or transfusion-dependent platelet counts < 20.000/μl or transfusion-dependent anemia. For these patients, CD34 selected stem cell boosts (SCB) from the same donor can be a treatment option. We here report our experience using SCB in patients with PGF.
Between 2006 and 2011, 20 patients received CD34 selected SCB at our institution. Indications for allogeneic HCT were ALL (n = 1), AML (n = 11), MDS (n = 1), NHL (n = 4) or PMF (n = 3). The cohort comprised 13 men and 7 women with a median age of 54 years at the time of transplantation (range 21–67 years). Seven patients had thrombocytopenia, another seven both thrombocytopenia and leukopenia, and 6 patients presented with tricytopenia. Poor graft function was confirmed and disease relapse excluded by bone marrow biopsy prior to donor mobilization. CD34+hematopoietic stem cells were isolated from G-CSF mobilized peripheral blood stem cells from leukapheresis products of the initial donor using the CliniMACS system from Miltenyi Biotech (Bergisch-Gladbach, Germany). Clinical and laboratory data of the patients were analyzed retrospectively.
An average of 4.32 ×106 CD34+ cells per kilogram bodyweight (1.6–9.1 ×106) with a purity of 97% CD34+ cells (63–99.5%) were transfused at a median of 133 days after HCT (47–1,568 days). An increase of leukocytes (median 3,100/μl, range 150–10,150/μl) was observed in 85% of the patients (n = 17). In 80% (n = 16) an increase of platelets (median 77,000/μl, range 7,000–223,000/μl), and in 55% (n = 11) an increase of hemoglobin (median 2 g/dl, range -1–5 g/dl) was induced through SCB. All patients benefitted from SCB in at least one hematopoietic line. Highest post-SCB values of leucocytes, thrombocytes and erythrocytes were reached on days 38, 59, and 55, respectively. Hence, efficacy of SCB could be best evaluated about eight weeks after transfusion. The mean T cell content of SCB was 0.2 ×104 (0.04–0.5 ×104) cells per kilogram bodyweight. No significant exacerbation or any primary manifestation of graft versus host disease (GvHD) was observed. Median follow-up time was 48 months (7–121 months) until death or last follow-up visit. At the end of follow-up, 11 patients were alive (55%) and 9 patients had died (45%). All patients alive remained disease free and transfusion independent and had stable leukocytes in normal range.
In patients with PGF and full donor chimerism after HCT, CD34 selected SCB can durably improve bone marrow function. Patients receiving SCB appear to have a very limited risk of developing or aggravation of GvHD. Of note, effects of SCB can clinically manifest up to eight weeks after transfusion. In conclusion, SCB are safe and effective in patients with PGF.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.