Late conversion to mammalian target of rapamycin inhibitor/proliferation signal inhibitors in kidney transplant patients: clinical experience in the last 5 years.

INTRODUCTION: Treatment with proliferation signal inhibitors (PSIs; sirolimus/everolimus) is a therapeutic option for renal transplant recipients, especially those who develop chronic graft nephropathy (CGN) or a neoplasm. We sought to analyze the efficacy and safety of conversion to PSIs. MATERIAL AND METHODS: We undertook a retrospective study of 77 patients converted between January 2005 and October 2009 to PSIs: 53 sirolimus and 24 everolimus. The causes for conversion were 63% tumors, 30% for chronic graft nephropathy (CGN), and 7% for other reasons. Mean time from transplant to conversion was 8 years. Patients were followed for a mean of 18 months (range, 1-61). RESULTS: A significant 14% improvement in renal function was observed at 1 year after conversion: baseline Modification of Diet in Renal Disease (MDRD) 45±20 versus 51±20.1 mL/min/1.73 m2 (P=.03). The benefit was greater among patients converted for CGN: baseline MDRD 31.5±8.8 versus 40.9±13.1 mL/min/1.73 m2 (P=.02), a 30% increase. The side effects experienced by 40% of patients included: 12% diarrhea, 15% edema, 20% buccal aphthae, 10% pneumonitis, and 20% skin alterations. PSIs were withdrawn in 25% of patients: 13% for side effects, 2.5% for patient death, and 3.8% for graft loss. We observed increases in serum lipids and proteinuria with a mild decrease in hemoglobin. CONCLUSION: Conversion to PSIs is a safe, useful therapeutic option for carefully selected patients, when renal function has not undergone marked deterioration and there is no proteinuria. Although side effects are common, most are mild; withdrawal of PSIs was necessary in a relatively low percentage of cases.

Does JC polyomavirus cause nephropathy in renal transplant patients?

INTRODUCTION: BK polyomavirus (BKV) reactivation characterized by active viruria occurs in 23%-57% of renal allograft recipients and BKV-associated nephropathy in as many as 8% of renal allograft recipients. Only a few cases of nephritis have been attributed to JC polyomavirus (JCV) with limited information about JCV replication and its impact on graft function and survival of kidney transplant patients. We sought to determine the prevalence of BKV and JCV replication, the risk factors associated with viral reactivation, and their implications for the development of polyomavirus nephropathy (PVN) among renal transplant patients. MATERIALS AND METHODS: The study included 186 kidney transplant recipients who were transplanted between 2005 and 2009 with a 1-year follow-up. If the urine polymerase chain reaction (PCR) was positive, we performed a PCR on blood. If this was positive or renal dysfunction was present, we performed a renal biopsy. RESULTS: Viruria was positive in 72 cases (39%) and viremia in 12 (6.5%); including, 3 patients (1.6%) who developed PVN. In the patients with viruria, BKV was detected in 47% and JCV in 46%; both were detected in 7%, although the combination of viremia and nephropathy were caused by BKV in all cases. CONCLUSION: In renal transplant patients, the incidence of BKV and JCV viruria was similar, although in our series the JCV serotype did not cause viremia or PVN. Our experience suggested that JCV did not have the ability to cause PVN.

Chronic lymphocytic leukemia is infrequent in Mexican mestizos.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults living in Western countries, and accounts for approximately 30% of adult leukemias. In a 15-year period in a single institution, we identified 19 patients with CLL in a group of 211 adults with leukemia (9% of adult leukemias). Of these 19 CLL patients, 8 had a Caucasian phenotype, 4 were born outside the country, and only 11 were Mexican mestizos. On the other hand, in a multicenter experience involving 1968 Mexican adults with leukemia, CLL represented 6.6% of the cases, a figure significantly lower than that reported in Caucasians (P < 0.01). CLL is the least frequent type of leukemia in Mexican mestizos, and this low prevalence may stem from the genetic origin of this racial group. The data also suggest a genetic predisposition of Caucasians to suffer from this disease.

Chemotherapy alone may be an efficient alternative in the treatment of early stage Hodgkin's disease if optimal radiotherapy is not available.

Because radiotherapy (RT) equipment technology in some developing countries is outdated, its side effects are more frequent and severe and its efficacy suboptimal, whereas chemotherapy (CT) meeting international standards is generally more consistent. With this in mind, we treated 29 patients with stages I and II Hodgkin's disease with the MOPP or the MOPP/ABV hybrid schedule without prior staging laparotomy. The complete remission rate was 96%: five patients relapsed and of these, two died and three were rescued with CT, in one case followed by an autologous stem cell autograft. The median follow-up is 54 months (range 9 to 126), the overall survival of the group 88% at 126 months, and the relapse-free survival 72% at 110 months. Conventional CT alone has been shown to be useful in achieving acceptable long-term results. This observation could be important in circumstances where RT is unavailable or of suboptimal quality.

[Results of the treatment of acute leukemia in adolescents]. / Resultados del tratamiento de leucemias agudas en adolescentes.

In the course of 120 months we have prospectively treated 45 patients with acute leukemia aged 11 to 21 years: 33 with acute lymphoblastic leukemia (ALL) and 12 with acute myelogenous leukemia (AML). Patients with ALL were treated with St. Jude's protocol XI: there were five early deaths and complete remission (CR) was achieved in 76% (89% of those completing one month of treatment); median survival (SV) was 29 months and the 120-month SV was 35%. AML patients with promyelocytic leukemia were induced to remission using all-trans-retinoic acid, whereas those with other types of AML were given the classic 7 + 3 scheme: the CR rate was 85%, median survival has not been reached and the 33 month survival was 72%. Four patients with AML were given peripheral blood stem cell autografts as part of the post-remission therapy. Our data in ALL and AML appeared to be intermediate to those in children and adults.

Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy premenopausal women: relationship with body weight regulation.

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, such as hypogonadism and hyperandrogenicity, may be involved in the excessive body weight gain induced by antipsychotic drugs in women. The present study was conducted in healthy premenopausal women, in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. After a control menstrual cycle, sulpiride (200 mg/day) or placebo was nonblindly administered for 28 days; blood lipids and the serum levels of the following hormones which are involved in body weight regulation were assessed at days 3, 10, 20 and 26 of the cycle: prolactin (PRL), 17-beta estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), cortisol, tyrotropic hormone (TSH), tetraiodothyroxine (T4), and the areas under the insulin and glucose tolerance curve. During sulpiride administration, the following changes were observed when compared to placebo administration: PRL levels were significantly increased; E2 levels were significantly reduced at days 10 and 20; P4 levels were significantly reduced at day 20, and the area under the glucose tolerance curve was significantly increased. The other variables were not significantly affected. The body weight gain was higher during sulpiride than during placebo administration, but it did not reach statistical significance, perhaps because the period of treatment was too short. The decrease in the serum levels of E2 during sulpiride administration is probably secondary to hyperprolactinemia. It affects the E2/T5 ratio in the direction of increasing the androgenic activity, as observed in women with well-established obesity. This effect, along with a genetic predisposition, increased appetite, hypoactivity and ignorance of proper dietary habits, may explain the excessive weight gain and obesity observed in women during chronic treatment with sulpiride and other antipsychotic agents.

Hairy cell leukemia is infrequent in México and has a geographic distribution.

Considering that the prevalence of some hematologic malignancies may have a geographic distribution that could be related with its etiology, a group of 2,387 patients with acute leukemia (1,968 adults and 419 children) was studied along a 5-year period in six different locations within México. Twenty-seven patients (16 males and 11 females) with hairy cell leukemia (HCL) were identified. The adjusted overall proportion of HCL, after excluding data from centers reporting only adults, was 1.12% of all leukemia cases; this figure is lower than that reported in the United States or England. The proportion of adult leukemic patients with HCL was significantly higher in the northern region of the country-where there are more people devoted to farming and agricultural activities-as compared with the central or southeastern regions (3.07 vs. 1.03% vs. 0%; P < 0.05); possible explanations for these differences are briefly discussed.

Filgrastim-mobilized peripheral-blood stem cells can be stored at 4 degrees and used in autografts to rescue high-dose chemotherapy.

We studied 21 filgrastim (G-CSF)-mobilized peripheral blood stem cells (PBSC) apheresis products obtained from seven patients, and stored at 4 degrees C for periods of up to 96 hr prior to their reinfusion, to rescue high-dose chemotherapy. The apheresis products contained a median of 106 x 10(8)/L mononuclear cells (MNC), 14.6% of them displaying the CD34 antigen; the viability was over 90% in all samples studied at 24, 48, and 72 hr after harvesting. These PBSC were successfully used to rescue high-dose chemotherapy; patients received a median of 4.8 x 10(8)/Kg MNC; the median time to achieve > 500 granulocytes was 14 days (range 11-26) and the median time to achieve > 20,000 platelets was 20 days (range 11-40). Since autologous transplants with nonfrozen PBSC are feasible and less costly than those using frozen PBSC, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.

Twenty-four adult patients with AML were treated with standard "7 + 3" chemotherapy. After administering the myeloablative drugs in the hospital, patients were instructed to continue their supportive treatment on an outpatient basis; they received ciprofloxacin, cotrimoxasole and itraconazole vo until the absolute granulocyte count rose above 1 x 10(9)/l. Platelet concentrates were given every other day until the platelet count rose above 20 x 10(9)/l. Complete remission (CR) was obtained in 87%. Fever developed in 29% and 2 cases were complicated by indwelling-catheter-related Pseudomona aeruginosa septicaemia, 1 Entamoeba hystolytica enteritis and 1 Pneumocystis carinii pneumonia; these patients were hospitalized to treat these infections specifically. In no case was the infection fatal. The median disease free-survival (DFS) was 17 months, 12-month DFS was 66%, and 30-month DFS was 17%. Our calculations have shown that 1700 USD/patient were saved by avoiding prolonged hospitalization; this may provide not only economical, but also psychological advantages to patients.

The infusion of anti-RhO-(D) opsonized erythrocytes may be useful in the treatment of patients, splenectomized or not, with chronic, refractory autoimmune thrombocytopenic purpura--a prospective study.

Six patients with chronic refractory autoimmune thrombocytopenic purpura (ATP) were treated with five doses of autologous red blood cells (RBCs) opsonized ex vivo with anti-RhO-(D) IgG. Increases in platelet counts were observed in all cases; complete responses requiring no further treatment--for periods of 8-72 months--were recorded in four patients, three of them splenectomized. The cost of the procedure was significantly lower than other "Fc receptor (FcR) blockade" treatments.