I. García

Marked reduction in the incidence of hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation with CD34(+) positive selection.

Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34+ positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34+ positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34+ positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT. Bone Marrow Transplantation (2001) 27, 983–988.

FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Forty-five patients with high-risk myeloid malignancies (32 acute myeloid leukemia and 13 high-risk myelodysplastic syndromes) were treated with fludarabine, cytarabine, idarubicin, and G-CSF (FLAG-IDA). Twenty-four (53%) patients achieved complete remission (CR), and five (11%) partial remission. Infection predominantly with pulmonary involvement was the most common regimen-related toxicity. Mucositis (15 patients) and pulmonary toxicity (19 patients) were the most frequently observed non-hematologic side effects. There were four early deaths and 12 patients presented with resistant disease. Overall survival (OS) at 12 months was 40%. The FLAG-IDA regimen shows evident antileukemic activity in patients with high-risk myeloid malignancies with acceptable toxicity.

Activity and safety of lenalidomide and dexamethasone in patients with multiple myeloma requiring dialysis: a Spanish multicenter retrospective study.

To the Editor: Lenalidomide is an immunomodulating agent that has been shown to be a highly active agent in the management of patients with multiple myeloma (MM) (1, 2), but most studies excluded patients with a serum creatinine level >2.5 mg ⁄dL. Experience with lenalidomide (3) in the management of patients with MM and renal impairment is scarce. We present the results of a retrospective study in a group of 15 patients from 11 Spanish centers with MM and severe renal impairment requiring dialysis and receiving lenalidomide-based therapy at the time of study entry. Response criteria were based on the International Myeloma Working Group (IMWG) criteria (4). Patient features at the time of inclusion are summarized in Table 1. Two patients had renal impairment requiring dialysis before myeloma diagnosis. The remaining thirteen patients developed renal failure at diagnosis or during the evolution of the disease, and it was because of MM (six patients), drug-related (two patients), secondary to underlying diabetes (two patients), and secondary to a tumoral lysis syndrome because of bortezomib (one patient). Finally, no data were available in the remaining two patients. Thirteen (86%) patients received lenalidomide at a dose of 15 mg ⁄d, three times a week after dialysis and in combination with dexamethasone (Table 1). Patients received a median of eight cycles (range, 1–28) of lenalidomide treatment. Hematological toxicity was the toxicity more frequently seen and required dose reduction in eight (53%) patients, and granulocyte-colony stimulating factor prophylaxis in seven (47%). Ten patients developed neutropenia (6 grade 3–4), and seven (47%) patients presented thrombocytopenia (1 grade 3). Finally, two (13%) patients presented grade 2 anemia. Six (40%) patients developed seven infectious episodes during the study period, five of them within the first four cycles of therapy. There were four (57%) bacteremias, two (29%) pneumonias, and one (14%) central venous line infection (Table 2). Other non-hematological complications are shown in Table 2. There were no thromboembolic complications. Overall response rate was 60% (nine patients), with four (29%) achieving complete response (CR), one (7%) patient very good partial response, and four (29%) patients partial response. Median time to best response was 4 months. With a median follow-up of 13 months (range 1–28), median progression-free and overall survival was 15 and 20 months, respectively. Among responding patients, median duration of response has not been reached. Seven (47%) patients have died because of disease progression (five patients) and of infectious complications (two patients) and eight (53%) are still alive, seven with continuous lenalidomde treatment and one off therapy because of disease progression. Renal function remained stable in all but one patient who was spared from dialysis after achieving partial response 3 months after starting treatment. Currently, there is no standard treatment for patients with MM and renal failure requiring dialysis. Results with new agents such as thalidomide and bortezomib are disparate. With thalidomide, experience is scarce and has been associated with a high incidence of hyperkaliemia in patients with serum creatinine >3 mg ⁄dL (5, 6). Better results have been reported with bortezomib-based regimens, with a response rate of 75% with 30% of CR + near CR and with a toxicity profile similar to that observed in patients with normal renal function (7). Lenalidomide has been shown to undergo substantial elimination via the kidneys, and recently, encouraging results have been reported in patients with different degrees of renal impairment (3). However, no data in patients with MM and advanced renal failure requiring dialysis are available. Our report is the first one including this high-risk subgroup of patients with MM and show a response rate of 65% with 29% of CR like that seen in patients with normal renal function (1, 2). Importantly, progression-free and overall survival was also similar to that reported in patients without significant renal failure (1, 2). Finally, among responding patients, median duration of response has not been reached, pointing that durability of response is also comparable to those of patients with MM with normal renal function in the relapsed setting (1, 2). In our series, as in other studies including lenalidomide in patients with mild renal impairment (3, 8, 9), doi:10.1111/j.1600-0609.2010.01500.x

Prospective Study of Infection and Nephropathy Due to BK and JC Polyomavirus in 76 Kidney Transplant Recipients

INTRODUCTION Nephropathy due to polyomavirus is usually diagnosed by renal biopsy after worsening of renal function. This is normally at an advanced stage of the disease. AIM To study the early detection of the presence of BK and JC polyomavirus in urine by monthly real-time quantitative polymerase chain reaction (PCR) assay. MATERIAL AND METHODS The study included 76 kidney transplant recipients from cadaveric donors between August 2005 and July 2006 with a 1-year follow-up. RESULTS Viruria was positive in 31 patients (40.7%) and viremia in 7 (9.2%), three of whom (3.9%) developed nephropathy. After reduction of the immunosuppression, the viruria became negative in 32.0% and the viremia in 42.8% of the patients. Renal function (creatinine clearance, aMDRD) at 1 year was 49.2 mL/min/1.73 m(2) in the patients with nephropathy and 64.3 mL/min/1.73 m(2) in the others. One-year patient and graft survival was 96%. No patient lost the graft due to nephropathy. CONCLUSIONS The detection of BK and JC polyomavirus by protocolized PCR enabled an early diagnosis of nephropathy, preventing graft loss with good renal function at 1 year.

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.

Biopsies in renal transplant patients with proteinuria: histological findings.

INTRODUCTION Proteinuria is related to a poor prognosis for graft survival. MATERIALS AND METHODS We undertook a retrospective study of renal transplant biopsies between 2006 and 2009 performed because of proteinuria. Data were collected on demographic, analytical, and histological characteristics. RESULTS The study included 49 biopsies from 65% men with an overall mean age of 52 ± 13 years. The mean time from transplant to biopsy was 6.5 ± 5.3 years. All cases displayed proteinuria: 2.2 g/24 h (1.2-3.2). In 56% of cases, it was also associated with worsening glomerular filtration rate (GFR) (MDRDa 33 ± 16 mL/min). In 14% of cases, the sample was insufficient to determine glomerular pathology, whereas 51% displayed glomerular disease, among which were transplant glomerulopathy (40%), glomerulonephritis (48%), and diabetes (12%). Interstitial fibrosis and tubular atrophy (IFTA) was present in 85%: 33% mild, 27% moderate, and 25% severe. Arteriolar hyalinosis was present in 60%. Thirty-four percent of subject lost their grafts at a mean of 11 ± 9 months after the biopsy. The GFR at the time of biopsy was worse among those subjects who returned to dialysis than those who retained function (MDRDa 22 ± 7.5 vs 34 ± 15 mL/min; P = .006). Proteinuria was also greater among those who lost their grafts (4.1 ± 3.4 vs 2.1 ± 1.6 g/24 h; P = .007). The absolute increase in the risk of graft loss was 52% among subjects who displayed moderate to severe versus those who had mild IFTA (relative risk [RR] 7; confidence interval [CI] 1.8-28; P < .001). The presence of glomerulosclerosis >50% was also associated with a 48% absolute increased risk of graft loss compared with those patients with no glomerulosclerosis or <50% (RR 3; CI 1.5-12; P = .02). After the biopsy, the dose of angiotensin converting enzyme inhibitors and/or angiotensin receptor antagonist was increased in 90%, with 34% of subjects, experiencing a change in immunosuppression. CONCLUSIONS Transplant patients undergoing a biopsy due to proteinuria, the occurrence of graft loss was associated with reduced GFR and the amount of proteinuria at the time of the biopsy, as well as with the degree of IFTA and of glomerular involvement.

Approximation of Continuous Media Models for Granular Systems Using Cellular Automata

In this paper a new cellular automata model suitable for granular systems simulation is presented. The proposed model is shown to be equivalent to a particularization of the well known BCRE model of granular systems and a correspondence between the parameters of the presented model and the BCRE model is also set, allowing to fit these parameters for a given system. The model has the advantage over other cellular automata models of being more realistic in the behavior of the surface of heaps and slopes. The dynamics of the CA is analyzed in order to confirm that it also has one of the most important features of these systems, 1/f noise.

Renal Transplantation in Old Recipients From Expanded Criteria Donors Selected by Kidney Biopsy

BACKGROUND In Spain, the number of ideal kidney transplant donors has fallen, with at the same time an increase in the number of older recipients on the waiting list. AIM To analyze the results of expanded criteria cadaveric donor kidney transplants into older recipients using grafts selected by kidney biopsy. PATIENTS AND METHODS We studied 360 kidney transplant recipients who had been followed to December 2009: 180 in the study group and 180 in a control group composed of younger patients who received grafts from non-expanded criteria donors between 1999 and 2006. A paraffin-embedded kidney biopsy was evaluated by the percentages of sclerosed glomeruli, arteriolar hyalinosis, intimal wall thickening, interstitial fibrosis, and tubular atrophy. RESULTS Significant differences were observed in donor age (63.50±5.46 vs 31.90±13.29 years; P<.001) and recipient age (58.40±8.80 vs 40.71±13.23 years; P<.001). Donor renal function was significantly worse among the expanded criteria group (90.80 vs 108.11 mL/min/1.73 m2; P=.006), remaining so over time in the recipient (at 1 year: 42.08 vs 63.71 [P<.001]; at 3 years: 41.25 vs 62.31 [P<.001], and at 7 years: 38.17 vs 64.18 [P<.001]). Censored 7-year graft survivals were 73% versus 87% (P<.001) with similar patient survivals (90.5% vs 95%; P=.39). CONCLUSIONS Selection of expanded criteria donors by kidney biopsy resulted in good renal function as well as graft and patient survivals at 7 years in older recipients.