Contemporary analysis of the influence of acute kidney injury after reduced intensity conditioning haematopoietic cell transplantation on long-term survival.

We evaluated retrospectively the incidence of acute kidney injury (AKI), defined by risk, injury, failure, loss and end-stage kidney disease (RIFLE) and its influence on long-term survival, in 82 patients aged 18-60 years who underwent a reduced intensity conditioning (RIC) haematopoietic cell transplantation (HCT). Patients (53.6%) developed AKI after HCT: 25% were on risk, 45.5% on injury and 29.5% on failure. In all, 64 patients survived after 100 days of post transplant and were available for long-term survival analysis. At follow-up, 43.7% of patients died. A 5-year overall survival of AKI patients was 41.6% as compared with 67.1% for those who did not develop AKI (P=0.028), and decreased according to AKI severity (risk, 55.6%; injury plus failure, 33.3%; P=0.045). After adjusting for age, history of cardiovascular disease, high-risk disease and chronic GVHD, AKI predicted 5-year overall mortality (AKI: adjusted hazards ratio (AHR), 2.36, 95% CI: 1.03-5.37; P=0.041). Moreover, moderate and severe AKI (injury plus failure) was also associated with an increased 5-year overall mortality (injury plus failure: AHR, 1.64, 95% CI: 1.06-2.54; P=0.024). According to RIFLE, 53.6% of patients had AKI after RIC HCT. Such patients have poor long-term survival, particularly in moderate or severe AKI.

Allogeneic stem cell transplantation in patients with myelodysplastic syndrome: outcome analysis according to the International Prognostic Scoring System.

We determined the outcome of patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after allogeneic stem cell transplantation according to their international prognostic scoring system (IPSS) risk categories at diagnosis. A total of 11 females and 7 males, with a median age of 45 years, were transplanted. With a median follow-up of 60 months, the 6-year actuarial event-free survival (EFS) for Less Advanced (Low and Intermediate-1 risk IPSS) and Advanced (Intermediate-2 and High risk IPSS) MDS was 71.4% and 43.6%, respectively (p=0.002). We did not observe a difference in EFS depending on cytogenetics at diagnosis (good risk 53.8% Vs intermediate and high risk 53.3%, p=ns), neither on the type of conditioning regimen used (myeloablative 50% Vs reduced intensity 52.2%, p=ns). Our results support that IPSS score at diagnosis may be used to predict EFS in patients with MDS undergoing allogeneic SCT.

Invasive aspergillosis of the central nervous system after allogeneic stem cell transplantation.

Central nervous system aspergillosis is a rare infectious complication in patients submitted to allogeneic stem cell transplantation. When it arises, this infection appears early post-transplant and most patients present with multiple central nervous system lesions. We report the clinical case of a 52 year old woman with IgGk multiple myeloma in relapse after a matched related allogeneic bone marrow transplant, who presented with a single large central nervous system Aspergillus lesion 11 months post-transplant in the setting of acute graft vs. host disease developing after the infusion of donor leucocytes. Although liposomal amphotericin B was promptly instituted, the patient died 1 week after the diagnosis.

Autologous stem cell transplantation in acute myeloid leukemia. Factors influencing outcome. A 13 year single institution experience.

We report our results of autologous stem cell transplantation (SCT) in patients with AML during the last 13 years. Between August 1990 and December 2003, 42 patients with acute myeloid leukemia (AML) received an autologous SCT. Patients were classified as standard risk if first complete remission (CR) was induced after one or two chemotherapy regimens and the white blood cell count at presentation was below 50,000/mL (n=12), while patients requiring more than two induction regimens to attain first CR and with CR2 ou more advanced disease and/or had a higher white blood cell count at presentation were defined as high risk (n=30). Twenty one patients were transplanted in first CR. The median patient age was 24 years (range, 2-56 years), and the median time interval from diagnosis to autologous SCT was 9 months (range 3-87 months). The conditioning regimen for SCT consisted of busulfan (BU) 16 mg/kg and melfalan (MEL) 180 mg/m2 (BUMEL) in 17 (40%) patients and busulfan 16 mg/kg and VP-16 60 mg/kg (BUVP16) in 22 (52%) patients. Three patients received a different conditioning regimen with BCNU 300 mg/m2, VP16 2 g/m2 and melphalan 160 mg/m2 (BEM). Twenty five (60%) patients received bone marrow (BM), 11 (26%) patients received peripheral blood stem cells (PBSC) and 6 patients (14%) received BM plus PBSC. With a median follow-up of 7 years, the 13 year overall survival (OS) and diseasefree survival (DFS) of all patients is 52% and 40%, respectively. In univariate analysis, males had a significantly superior DFS than females (55% vs 22%, p=0.003), and patients younger than 15 years of age had significantly superior OS and DFS than older patients (50% vs 35%, p=0.05; and 50% vs 28%, p=0.03, respectively). Patients with FAB M3 subtype also had a superior OS than the other FAB subtypes (100% vs 44%, p=0.05). There was a strong statistical correlation between risk group and survival. In fact, the patients with standard risk had a superior OS and DFS than those with high risk disease (67% vs 23%, p=0.0004; and 50% vs 27%, p=0.01, respectively). When patients with FAB M3 disease were excluded from the analysis, the group with standard risk continue to have a superior OS and DFS (67% vs 13%, p=0.008; and 50% vs 14%, p=0.02, respectively). We conclude that autologous SCT is an effective treatment in AML with the possibility of long survivorship, particularly in patients with standard risk disease.

Haploidentical stem cell transplantation with purified CD34 cells after a chemotherapy-alone conditioning regimen.

We investigated whether a novel chemotherapy-alone conditioning regimen would permit durable engraftment of standard doses of CD34+ purified stem cell grafts from full-haplotype mismatched related donors. We also examined the role of infusing limited doses of donor leukocytes for prevention of leukemia relapse. Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14 patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of 6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6) CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4) CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus-host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late graft rejections were observed. All surviving patients received at least 1 infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells per kilogram between days 25 and 95 after transplantation, after which 8 developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2 developed a bronchiolitis obliterans-like syndrome. After attaining complete remission, 5 patients relapsed and died with active leukemia. The estimated relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14 patients have survived a median of 43.5 months after transplantation with 100% donor cells. All 6 surviving patients developed acute GVHD and had a natural killer cell mismatch with their donors in the direction of graft versus host. The estimated overall survival and event-free survival for the 14 patients at 4 years is 41.7% +/- 13.5%.