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%.

Follow-up of anti-Aspergillus IgG and IgA antibodies in bone marrow transplanted patients with invasive aspergillosis.

A total of 89 patients at risk for, or with invasive aspergillosis (IA) were recruited from bone marrow transplantation (BMT) units in two Lisbon hospitals, and followed for 2(1/2) years to monitor their immune response. Of these patients, six developed probable IA, from which five died. The presence of serum IgG or IgA antibodies against seven Aspergillus recombinant antigens was assessed in patients with IA, using an enzyme-linked immunosorbent assay (ELISA). In parallel, the serum levels of galactomannan (GM) were also monitored, using the Platelia Aspergillus kit (Sanofi Pasteur, Marnes-la-Coquette, France). Superoxide dismutase (Sod) and 94 kDa were the most immunogenic antigens for IgA, while the IgG pattern of recognition changed from patient to patient. From our results we conclude that although follow-up of antibodies against these antigens should not be used as a diagnostic method, patients with IA do produce an immune response that may influence disease outcome.

Parenteral nutrition and cyclosporine: do lipids make a difference? A prospective randomized crossover trial.

AIMS: This prospective, controlled, randomized crossover trial was conducted to assess the effects of parenteral nutrition, with or without lipids, in cyclosporine (CyA) pharmacokinetics. METHODS: 10 adult patients were randomized on the day of allogeneic bone marrow transplantation to receive isocaloric and isonitrogenous parenteral nutrition admixtures without (regimen A) or with lipids (regimen B). Admixtures were started on average by day + 7.4; 5 patients received regimen A followed by B, 5 in reverse order. Blood samples were collected at day 4 after transplantation, under oral diet, and 4 days after the initiation of each regimen as the sole nutrition support. At each time point, 8 whole blood samples were analysed for CyA to evaluate: area under the curve (AUC), trough concentration and systemic clearance. Clinical/laboratory events were recorded until 31 months of follow-up. RESULTS: There was no evidence of a period or treatment-by period interaction, thus results were combined for further analysis. There were no statistically significant differences between regimens in any CyA pharmacokinetic parameters; there were no significant differences from baseline values, except for a higher systemic clearance of CyA with regimen A (0.40+/-0.09 vs 0.29+/-0.06 L/Kg/h, p=0.03). CONCLUSIONS: The provision of 0.8 g/Kg/d of a 50:50 mixture of medium and long chain triglycerides did not affect CyA parameters, which were closer to baseline. In the short or long term there were no attributable side effects.

[Aplastic anemia. Alternative treatment by bone marrow transplantation]. / Anemia aplástica. Tratamento alternativo à transplantação medular.

We report a case of a 25-year-old woman, with the diagnosis of severe aplastic anemia without a histocompatible sibling donor for bone marrow transplantation. The patient has been treated successfully with a combination of two immunosuppressive agents, cyclosporine and antilymphocyte globulin, after not responding to primary therapy with corticosteroids and growth factors. She showed a complete response to treatment, with transfusional independence, after a follow-up of 14 months. The pathophysiology of aplastic anemia, the mechanism of action and secondary effects of these treatments are discussed.

[Treatment of acute promyelocytic leukemia with trans-retinoic acid. Experience of the Santa Maria Hospital, Medical School of Lisbon]. / Terapêutica da Leucemia promielocítica aguda com ácido Trans-Retinóico. Experiência do Hospital de Santa Maria, Faculdade de Medicina de Lisboa.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia that is usually associated with a fatal hemorrhagic diathesis. All trans-retinoic acid (ATRA) is an active metabolite of vitamin A that differentiates the malignant cell clone, corrects the coagulopathy, and induces complete remission in the vast majority of patients with APL. Between June 1992 and September 1993, 8 patients with APL (4 previously untreated, 3 in first relapse and 1 in second relapse) received ATRA. Complete remission was achieved in 7 patients; in 5 with ATRA alone and in 2 with ATRA followed by cytotoxic chemotherapy due to the development of asymptomatic hyperleukocytosis. The earliest signs of response were the correction of the coagulopathy and an increase in the white blood cell count. Sequential morphological and immunophenotypical analyses of the bone marrow revealed differentiation of the malignant cell clone, in the absence of bone marrow hypoplasia. 4 of 5 patients treated only with ATRA until complete remission had late leukopenia. The most frequent adverse effects were dryness of skin and mucosae, hypertrigliceridemia and hypercholesterolemia, and a moderate increase in liver transaminases. An increase in the white blood cell count was common, and in two cases exceeded 35.0 x 10(9)/l. One of these patients developed multiple thrombosis of the extremities after cytotoxic chemotherapy. We frequently observed an increase in lactic dehydrogenase levels that was concomitant with the peak in the white blood cell count. The only patient on whom complete remission was not achieved was 60 years old, had chronic obstructive pulmonary disease, and died in the third week of therapy with a pulmonary distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute promyelocytic leukemia. The therapeutic advances]. / Leucemia promielocítica aguda. Avanços terapêuticos.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia. It is frequently associated with a life-threatening hemorrhagic diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with APL have bone marrow infiltration by abnormal promyelocytes, usually with prominent cytoplasmic granulation. These patients have a unique cytogenetic abnormality, a balanced reciprocal translocation between the long arms of chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on chromosome 17, is translocated to the PML gene region, on chromosome 15, resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR-alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase chain reaction. This assay is extremely useful in the diagnosis and detection of minimal residual disease in APL patients. All trans-retinoic acid (ATR) differentiates the malignant cell clone and corrects the coagulopathy associated with this disease. The most important adverse effect is a respiratory distress syndrome, treatable with steroids, if detected at its onset. ATR yields durable remissions in patients with APL, after consolidation with cytotoxic chemotherapy.

[Methods for preserving bone marrow for autologous transplantation]. / Métodos de conservação de medula óssea para transplantação autóloga.

For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.

[Bone marrow transplantation. Preliminary results]. / Transplantação da medula óssea. Resultados preliminares.

From May 1989 to March 1991 60 bone marrow transplants were performed--41 allogeneic and 19 autologous--in patients with malignant and nonmalignant hemopathies and solid tumors. The transplant related mortality was 19.4% and 10.5% for allografts and autografts, respectively. The projected relapse free survival at 22 months in patients with malignant hemopathies who underwent allotransplantation in early phase was 81% and, in patients in advanced phase 21.4% (p less than 0.001). In patients with aplastic anemia the actuarial survival at 22 months is 60%. In autografted patients, only one failed to have full engraftment and is dependent on platelet support at day 79. Follow-up in all autografts is less than one year. These preliminary results of our bone marrow transplant program show low morbidity and mortality related to transplantation and suggest significant therapeutic effect.

[Psychiatric disorders in hospitalized patients with hematologic neoplasms]. / Distúrbios psiquiátricos em doentes internados com neoplasias hematológicas.

We report the results of a year of regular psychiatric support in the Hematology Department (UTI-DH) at Santa Maria Hospital. During a six-month period, the total group of hospital inpatients suffering from leukemia, Hodgkin's disease or non-Hodgkin's lymphoma, were assessed, using a semi-structured interview. A prevalence of 30% of adjustment disorders (depression and/or anxiety) and 2% of organic mental syndromes was found employing the DSM-III-R diagnostic system. In the second six-month period only patients referred by their doctor and/or nurse were observed. The two rates are discussed. A lower prevalence was found if compared with other studies in cancer patients in general. Possible causes will be focussed. General problems related to the nature of the cancer were identified. The consequences of the omission of cancer diagnosis to patients are analysed. The communication between physician and patient which is often neglected irrespectively of the culture or country, is stressed.