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.

Severe Acute Anemia After Liver Transplantation in an Elderly Jehovah's Witness Treated With High-dose Erythropoietin and Ferric Carboxymaltose: A Case Report.

BACKGROUND: There is no standard treatment for patients with severe anemia who refuse blood transfusion or cannot receive red blood cells. CASE REPORT: After an orthotopic liver transplantation, an elderly Jehovah's Witness who refused blood transfusion presented with severe acute anemia with hemorrhagic shock. The calculated red blood cell loss was near 70%. Associated with surgical treatment and supportive measures, the patient was treated with high-dose erythropoietin and ferric carboxymaltose. RESULTS: The patient presented a rapid increase in hemoglobin concentration and reticulocyte count with resolution of hemorrhagic shock after the proposed pharmacologic treatment combined with local hemostatic measures. She was transferred to a low-risk unit 4 days after transplantation and was discharged from the hospital on day 10. The hemoglobin concentration was normal 35 days after the bleeding event. CONCLUSION: This case demonstrated that a protocol with high-dose erythropoietin and ferric carboxymaltose may be an option for patients with severe anemia who refuse blood transfusion or cannot receive red blood cells.

Differentiation syndrome in promyelocytic leukemia: clinical presentation, pathogenesis and treatment.

Differentiation syndrome (DS) represents a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (ATO). It affected about 20-25% of all patients and so far there are no definitive diagnostic criteria. Clinically, DS is characterized by weight gain, fever not attributable to infection, respiratory distress, cardiac involvement, hypotension, and/or acute renal failure. At the histological point of view, there is an extensive interstitial and intra-alveolar pulmonary infiltration by maturing myeloid cells, endothelial cell damage, intra-alveolar edema, inter-alveolar hemorrhage, and fibrinous exsudates. DS pathogenesis is not completely understood, but it is believed that an excessive inflammatory response is the main phenomenon involved, which results in increased production of chemokines and expression of adhesion molecules on APL cells. Due to the high morbidity and mortality associated with DS, its recognition and the prompt initiation of the treatment is of utmost importance. Dexamethasone is considered the mainstay of treatment of DS, and the recommended dose is 10 mg twice daily by intravenous route until resolution of DS. In severe cases (respiratory or acute renal failure) it is recommended the discontinuation of ATRA or ATO until recovery.

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.