Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression in patients with acute lymphoblastic leukemia - update of single center study.

Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute graft versus host disease (GVHD) as well as the chronic one were equally observed in four cases (16%). Five patients (20%) relapsed with ALL in the median of 9 (range, 3-15) months after HSCT. During the above post-transplant follow-up, 4 recipients (16%) died. Disease progression and posttransplant complications were the cause of death in three (12%) and one (4%) of them, respectively. The probabilities of 2-year event-free (EFS) and overall survival (OS) were 70.3% (95% CI 51.9-88.7%) and 86.1% (95% CI 71.6-100%), respectively. Presented study confirmed our previously reported promising results and this approach may be considered as an alternative to traditional HSCTs performed in high-risk patients with ALL.

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia.

Presented are results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 13 patients with high-risk acute lymphoblastic leukemia (ALL) in the first complete remission after a reduced intensity conditioning combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg). The immunosuppressive effect of T-cell depletion reducing the risk of graft-versus-host disease (GVHD) and non-relapse mortality was compensated by early initiation of reduction and withdrawal of prophylactic immunosuppression aimed at maintaining effective immunological antileukemic control. The median post-transplant follow-up was 23 (range, 10-65) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute GVHD was observed in two cases (15.4%); the chronic form was not noted. Two patients (15.4%) relapsed with ALL at 3 and 16 months after transplantation. During the above post-transplant follow-up, all 13 recipients were alive, with a probability of 2-year disease-free survival of 76.9% (95% CI 51-100%). Although the results were obtained with a small pilot study group it may be assumed that, given the prognostic risk of most patients and the nearly 2-year median post-transplant follow-up, the approach may be considered as an alternative to HSCTs after traditional myeloablative or reduced conditioning regimens with standard GVHD prophylaxis.

[Toxoplasmosis after immunosuppressive therapy--our experience]. / Toxoplazmová infekcia u pacientov po transplantácii krvotvorných buniek--skúsenosti jedného pracoviska

Toxoplasmosis is a parasitic disease associated with high mortality in immunocompromised patients. It may lead to life-threatening conditions, usually neuroinfections, pneumonia or disseminated disease. It may be potentially dangerous, especially for patients with prolonged lymphopenia or those treated with immunosuppressive drugs. In our centre, we have observed 3 cases of toxoplasmosis in patients after allogeneic haematopoietic stem cell transplantation (HSCT) (2.6% of 116 allo-HSCT patients since 2000) and one case after autologous HSCT (0.3% of 395 auto-HSCT patients since 1997). Toxoplasmosis is manifested by neurological symptoms including hemiparesis and paraparesis, cerebral salt-wasting syndrome (hyponatraemia and hypoosmolality), psychoorganic syndrome and signs of respiratory infection. The diagnosis was made by combining clinical signs and results of PCR and CT examinations. The patients were treated with high-dose pyrimethamine, clindamycin, co-trimoxazole and folic acid. Three of the four patients have survived with no signs of the disease. One patient died prior to treatment. The increasing use of highly immunosuppressive chemotherapy and conditioning regimens (including rituximab, fludarabine and anti-thymocyte globulin) is associated with a significant risk of toxoplasmosis. Variable manifestations, non-specific results of MRI or CT examinations and possibility of PCR negativity are the main obstacles to successful diagnosis.