Autologous hematopoietic stem cell transplantation for acute myeloid leukemia - single center experience.

We aimed to determine the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on acute myeloid leukemia (AML) patients as a valid alternative therapeutic option for patients without HLA-compatible donor. This retrospective single center study included 79 patients with AML older than 18 years. In this report, we describe the patient characteristics, engraftment, toxicity of treatment, complications, overall survival, and relapse incidence of 79 patients treated chemotherapy and followed by auto-HSCT. The descriptive statistics was used, and the method of Kaplan and Meier was applied to calculate the actuarial rate of overall survival. The patients achieved an absolute neutrophile count (ANC) of ≥ 0.5 x109/l in between 10 to 40 days; median was 14 days after auto-HSCT. The patients achieved platelet count ≥ 20 x109/l in between 10 to 209 days; median was 19 days after auto-HSCT. Hundred-day mortality after autologous transplant was 6.57% (5/76). The relapse rate was 39.5% (32 patients) and 7 patients (8.6%) were lost from follow-up. On the date of evaluation (April 30, 2016), 48 patients (60.8%) were alive, including 7 (8.6%) patients who are lost from follow-up (not responding to check-up request). The 5-year overall survival (OS) was 60.8%; median overall survival was not reached. The present clinical study has demonstrated safety and efficacy of myeloablative chemotherapy followed by auto-HSCT in the treatment of AML in first remission.

Graft-versus-host disease management.

Graft-versus-host disease (GVHD) remains a major problem of allogeneic hematopoietic-stem cell transplantation (HSCT) and an obstacle for successful outcome. Clinically significant acute GVHD (grade II or higher) developed in 20 to 65 percent of the patients. Death due to this complication accounts for approximately 50 percent of the deaths that are not due to a relapse of the neoplasm. Up to 70 % of patients who survive beyond day 100 develop chronic GVHD and it is the leading cause of nonrelapse mortality more than 2 years after allogeneic HSCT. In addition, chronic GVHD is associated with decreased quality of life, impaired functional status, and ongoing need for immunosuppressive medications. The incidence of chronic GVHD is increasing because of expansion of the donor population beyond HLA-identical siblings, older recipient age, use of peripheral blood cells as the graft source, and infusion of donor lymphocytes for treatment of recurrent malignancy after HSCT. With the current rush in new findings related to GVHD, we see a significant advancement in its management. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of GVHD, as access to the most sophisticated advances may vary depending on local circumstances (Tab. 4, Fig. 1, Ref. 51).

Treatment difficulty with acute GVHD - frequent cause of mortality after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Acute graft-versus-host disease (aGvHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: In this study, we have retrospectively evaluated the major risk factors for the development of aGvHD in 100 patients who underwent allogeneic transplantation at the University Hospital in Bratislava between January 2007 and December 2011. RESULTS: 29 patients acquired acute GvHD (Grade I - 12 patients, G II - 5 , G III - 3, G IV - 9). We proved a higher incidence of developing aGvHD in patients with unrelated donor type, TBI conditioning and cyclosporine (CsA) replacement with mycophenolate mofetil due to CsA nephrotoxicity, while other risk factors such as older patient age, the use of peripheral blood progenitor cells and donor/recipient sex mismatch were without statistical significance. The average time of onset of aGvHD has been 57 days (range 13-260) after HSCT. Corticosteroids were used as standard initial therapy with 52 % complete response (CR) rate, although the likelihood of response rapidly decreased with increasing severity of disease (G IV - 100 % refracterness). The response to primary therapy also correlated with overall survival. Patients with steroid-refractory aGvHD received a different second-line therapies (antithymocyte globulin, anti-TNFα antibody, anti CD52 antibody) with response rate 45 % (CR - 18 %, PR - 27 %). CONCLUSION: Outcome for the patients with steroid-refractory aGvHD was poor, disease very often returned or progressed with one year mortality rate 81 % , that represents an important therapeutic problem (Tab. 2, Ref. 10).

The feasibility of an early hospital discharge following chemotherapy for the acute myeloid leukemia.

OBJECTIVE: The hospitalization of the patient during the critical myelosuppressive period after chemotherapy is often complicated by infections caused by nosocomial pathogens, what is associated with a high antibiotics consumption and with prolongation of the period of hospitalization. These findings have led many centres to change their policy from "in-hospital" to "out-hospital care". In this retrospective study we tried, on the basis of our experiences, to identify the feasibility and safety of this approach. PATIENTS AND METHODS: We studied 56 patients with the acute myeloid leukemia treated in our clinic with the consolidation chemotherapy. We compared two groups of patients. In the first group, the patients were discharged upon completion of chemotherapy, consequently followed up as outpatients. Patients in the second group were observed in hospital during the entire nadir. Following 41 courses, patients were discharged and instructed to return immediately if fever or any other change of their clinical status occurred. RESULTS: In 24 cases after chemotherapy, the patients returned to the hospital after a discharge (in 23 cases because of fever), in 17 cases of nadir periods the hospitalisation was not necessary at all. Seven patients were readmitted in septic shock, but rapidly recovered. Two other patients died, one due to an irreversible shock within 12 hours of readmission and one due to bacterial meningitis within 48 hours after readmission. In 10 cases of rehospitalization, patients responded to the first line of antibiotics. In the second group of the patients, only 2 courses of consolidation from a total of 15 were not complicated. In contrast to the first group, we detected only poor effectiveness of broad-spectrum antibiotics in the group of inpatients. CONCLUSIONS: For AML patients in a good clinical status without any complicating medical conditions, the early discharge is feasible, safe and cost saving option (Tab. 2, Fig. 2, Ref. 7).

Granulocyte transfusions.

Neutrophils play an essential role in the defense of the body against bacterial and fungal infections. Disorders of their number or function significantly increase the risk of life-threatening infection. In spite of the development of growth factors, new broad spectrum antibiotics and antifungal drugs against nearly all known pathogens, severe neutropenia associated with bacterial or invasive fungal infections remains a major cause of morbidity and mortality in patients undergoing aggressive cancer chemotherapy or hematopoietic stem cell transplantation. Lately, an interest about granulocyte transfusions was renewed, what is a logical approach in the management of patients with prolonged 'reversible' severe neutropenia and severe infection, which is not controlled with appropriate antimicrobial and supportive treatment, including recombinant hematopoietic growth factors. It was a consequence of advances in the field of apheresis science, use of sedimenting agents and especially advances in mobilization of granulocytes to the peripheral blood. It became now possible to collect large numbers of neutrophils. Therefore, the clinical use of granulocyte transfusions, as a potential life saving treatment option in patients with severe neutropenia and uncontrolled infection in spite of appropriate antimicrobial therapy should be considered, with regard to possible benefits and risks (Ref. 74).