Mesenchymal stromal cell infusion to treat steroid-refractory acute GvHD III/IV after hematopoietic stem cell transplantation.

Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, ∼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6.81 × 106/kg (range, 0.98-29.78 × 106/kg) in a median of 3 infusions (range, 1-7). Median time between the onset of aGvHD and the first MSC infusion was 25.5 days (range, 6-153). Of the patients, 50% (23/46) presented clinical improvement. Of these, 3 patients (13%) had complete response, 14 (61%) had partial response and 6 (26%) had transient partial response. The estimated probability of survival at 2s year was 17.4%. Only 2 patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion. No patient had late or severe side effects because of MSC infusion. These results suggest that this therapeutic modality is safe and should be considered for steroid-refractory aGvHD, especially in countries where other second-line agents are less available.

Haematological recovery in poor and good haematopoietic stem cell mobilisers.

OBJECTIVES: Evaluate whether poor mobilisers had delayed haematopoietic (neutrophil and platelet) recovery despite receiving similar cell dose as good mobilisers. BACKGROUND: Autologous haematopoietic progenitor cell (HPC) transplantation is indicated to treat some haematological malignancies. This procedure requires HPC mobilisation from bone marrow to peripheral blood. Cell dose is important for a fast haematological recovery. Despite being poor mobilisers, some patients can collect enough cell numbers for transplantation. RESULTS: Fifteen poor mobiliser patients (peak of CD34+ cells ≤10 µL(-1) in peripheral blood) were transplanted at our institution. Haematological recovery (neutrophil ≥ 500 µL(-1) ) in this group was compared to that observed in the group of 16 patients of good mobilisers (peak of CD34+ cells ≥20 µL(-1) in peripheral blood) who received similar cell dose (2·637 ± 0·1744 × 10(6) kg(-1) vs 2·727 ± 0·1746 × 10(6) kg(-1) ; P = 0·7177). The poor mobiliser group had neutrophil and platelet recovery later than the good mobiliser group (on day 12, range 9-14 vs day 10, range 9-22, P = 0·0381 for neutrophil, and on day 22·89 ± 11·16 and 14·08 ± 4·821, P = 0·0193 for platelet). Mortality rates and transfusion requirements were not different between the groups. CONCLUSION: Poor mobilisers have delayed neutrophil and platelet recovery after autologous HPC transplantation despite having received the same cell dose as good mobilisers.

Outcome of acute myeloid leukemia patients with hyperleukocytosis in Brazil.

Acute myeloid leukemia (AML) with a high white blood cell (WBC) count at presentation has been associated with an increased early mortality rate, usually secondary to leukostasis. However, the value of the WBC count at which there is a high risk of early death (ED) and the efficiency of supportive treatments remain unclear. In this report, a series of 187 consecutive adult patients with AML in our institution was reviewed. The outcome of 40 patients with WBC above 50×10(9) L(-1) (hyperleukocytosis) was compared to 147 patients with a leukocyte count lower than 50×10(9) L(-1). The group with hyperleukocytosis showed a significantly shorter OS (P<0.0001) and a higher rate of ED (P=0.0008). Even when the data from ED patients were removed from analysis, we still detected a shorter OS in patients with hyperleukocytosis (P=0.0049), which suggests that high WBC number influences long-term survival, and not only ED. We also observed higher lactic dehydrogenase (LDH) and serum creatinine levels in the group of patients with hyperleukocytosis (P=0.0003 and 0.0406, respectively). Besides considering all the patients with ED, we could observe higher levels of lactic dehydrogenase, a serum creatinine and nitrogen urea (P=0.0056, P=0.0008 and P<0.0001, respectively). Pulmonary involvement was more frequent in patients with ED (P=0.0277). In conclusion, hyperleukocytosis confers a poorer prognosis in patients with AML.

Age-associated changes of memory (CD45RO+) and naive (CD45R+) T cells

The total number of lymphocytes and the percentage of CD45RO+ (putative memory T cell) and CD45R+ (putative naive T cell) were determined in 15 cord blod samples, 66 healthy children ranging in a age from 1 to 18 years, 16 adults (23-59 years) and 16 aged individuals (60-96 years). The total number of lymphocytes decreased with age and reached the adult range in children to the adult group,white the percentage of CD45RO+ Tcells was low in cord blood and increased with age.No significant difference was observed between the adult and the aged groups for either lymphocyte subset. These data support the view that CD45RO+ and CD45R+ T-cell subsets represent maturational stages of T cells

Age-associated changes of memory (CD45RO+) and naive (CD45R+) T cells.

1. The total number of lymphocytes and the percentage of CD45RO+ (putative memory T cell) and CD45R+ (putative naive T cell) were determined in 15 cord blood samples, 66 healthy children ranging in age from 1 to 18 years, 16 adults (23-59 years) and 16 aged individuals (60-96 years). 2. The total number of lymphocytes decreased with age and reached the adult range in children aged 11-14 years. CD45R+ T cells were the predominant cell type in cord blood and decreased with age up to the adult group, while the percentage of CD45RO+ T cells was low in cord blood and increased with age. No significant difference was observed between the adult and the aged groups for either lymphocyte subset. 3. These data support the view that CD45RO+ and CD45R+ T-cell subsets represent maturational stages of T cells.