Nuevas inmunoterapias en el cáncer de vejiga no músculo-invasivo de alto riesgo: estado actual y perspectivas de futuro / New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives

CONTEXTO: El tratamiento estándar de los tumores de vejiga no músculo-invasivos (TVNMI) de alto riesgo es la resección transuretral de vejiga e instilaciones de bacilo de Calmette-Guérin (BCG). Sin embargo, las respuestas son limitadas. Es necesario buscar nuevas alternativas terapéuticas para estos pacientes. Los resultados en tumores avanzados de los inhibidores de puntos de control han dado lugar al interés en el uso de estas moléculas en TVNMI. MÉTODOS: Hemos realizado una búsqueda en PubMed utilizando los términos «bladder cancer» y «check point inhibitors». Para la búsqueda de ensayos clínicos, hemos utilizado los buscadores clinicaltrials.gov y clinicaltrialsregister.eu RESULTADOS: Actualmente hay 5 ensayos en marcha de pacientes no tratados con BCG. No hay resultados disponibles. En cuanto a los pacientes no respondedores a BCG, existen 15 ensayos en marcha, 2 de ellos con resultados preliminares: el Keynote 057, con resultados prometedores con pembrolizumab y que ha llevado a la FDA a aprobar su uso en enero de 2020 y el SWOG S1605, que ha mostrado resultados similares con atezolizumab. Otros ensayos administran estos fármacos intravesicalmente, una opción atractiva si resulta efectiva para el control oncológico. CONCLUSIONES: Los inhibidores de puntos de control ofrecen una nueva posibilidad para los pacientes no respondedores al BCG. Probablemente en el futuro se podrán usar en pacientes no tratados previamente con BCG. Los datos preliminares de ensayos clínicos muestran resultados prometedores. Es importante un buen conocimiento de estas moléculas por los urólogos y la formación de equipos multidisciplinares para ofrecer las mejores alternativas terapéuticas a estos pacientes

BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer» and «check point inhibitors». We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients

New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives. / Nuevas inmunoterapias en el cáncer de vejiga no músculo-invasivo de alto riesgo: estado actual y perspectivas de futuro.

BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer¼ and «check point inhibitors¼. We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients.

Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry.

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.

Influence of donor age in allogeneic stem cell transplant outcome in acute myeloid leukemia and myelodisplastic syndrome.

The impact of donor age in patients with acute myeloid leukemia and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplant (HSCT) remains unclear. In the current study, we evaluate 179 consecutive patients who received an HSCT, from January 2000 to January 2013, in our Institution. Most of the HSCT (91%) were HLA-matched. Patient and donor median age were 51 years (18-69) and 47 years (12-75) respectively, and 81 donors (45%) were older than 50 years. The median follow-up was 38 months (range 1-138), Kaplan-Meier estimated 3-year overall survival (OS) was 63% and disease free survival (DFS) was 56%. Interestingly, patients who received an HSCT from a donor older age (>50 y) showed a poorer OS (51% vs 73%; p=0.01), as well as a higher TRM (20% vs 8%; p=0.038) and higher relapse rate (28% vs 39%; p=0.03). In a stratified subanalysis, 3-year estimated OS was significantly lower among patients undergoing an HSCT from >50 years sibling donors compared to those receiving an HSCT from <50 years unrelated donor (54% vs 72%; p<0.001). In summary, we can conclude that receiving an HSCT from a donor over 50 years old is associated with poorer outcome in patients diagnosed with MDS and AML, and this information may be incorporated into the complex process of donor selection.

Análisis coste-efectividad de las principales herramientas diagnósticas en mujeres con vejiga hiperactiva: historia clínica, diario miccional y estudio urodinámico / Cost-effectiveness analysis of main diagnosis tools in women with overactive bladder. Clinical history, micturition diary and urodynamic study

Objetivos: El presente trabajo de investigación clínica pretende analizar a la luz de la mejor evidencia científica el rendimiento y el coste de las principales herramientas utilizadas en el diagnóstico de la vejiga hiperactiva (VH). Métodos: Se trata de un estudio transversal exploratorio y analítico, en el cual se seleccionó una muestra de 199 mujeres diagnosticadas de VH entre los años 2006 y 2008, a las que se realizó de forma prospectiva: exploración física, análisis de orina, diario miccional (DM) y estudio urodinámico (EUD). Se asumió que un porcentaje de diagnóstico altamente sensible debería ser 80% y que una diferencia de diagnóstico del 10% entre las pruebas sería clínicamente relevante. Se determinó estadísticamente la sensibilidad de cada una de las pruebas de forma aislada y combinada para el diagnóstico de VH y una valoración de los recursos económicos directos e indirectos que conlleva su realización, analizándose el coste efectividad de la historia clínica (HC), DM y EUD para el diagnóstico de VH. Resultados: La sensibilidad global para el diagnóstico de VH es baja para cualquiera de las pruebas utilizadas de forma aislada, mientras que la combinación de 2 pruebas cualesquiera presenta una buena sensibilidad global para su diagnóstico. La combinación de HC y DM es la alternativa más coste efectiva en el diagnóstico de VH. Conclusiones: El uso de HC y DM es una combinación tan sensible para el diagnóstico de la VH como la asociación de cualquiera de ellas con el EUD, presentando además un menor coste económico

Objetives: The aim of the present clinical research is to analyze, in the light of the best scientific evidence, the performance and the cost of the main diagnostic tools for overactive bladder (OAB). Methods: It is an exploratory transversal study in which 199 women diagnosed of OAB between 2006 and 2008 were selected and underwent to following prospective analyses: physical examination, urine analysis, micturition diary (MD) and urodynamic study (UDS). A percentage of 80% was assumed as highly sensitive and a diagnostic difference among tests of 10% would be considered clinically relevant. Tests’ sensitivity for diagnosis of OAB was statistically established by two ways: isolated and combined. Besides, the direct and indirect costs of these tests performance were conducted. Cost-effectiveness study of clinical history (CH), MD and US for the diagnosis of OAB was performed. Results: Overall sensitivity for OAB diagnosis is low for the 3 tests used in isolated way, whilst the combination of any two tests shows good overall sensitivity. The combination of CH and MD has appeared as the most cost-effective alternative to OAB diagnosis. Conclusions: For OAB diagnosis, CH-DM combination shows the same sensitivity than the association of either of them with the UDS, but unlike to these, it shows the lowest cost

Cost-effectiveness analysis of main diagnosis tools in women with overactive bladder. Clinical history, micturition diary and urodynamic study.

OBJECTIVES: The aim of the present clinical research is to analyze, in the light of the best scientific evidence, the performance and the cost of the main diagnostic tools for overactive bladder (OAB). METHODS: It is an exploratory transversal study in which 199 women diagnosed of OAB between 2006 and 2008 were selected and underwent to following prospective analyses: physical examination, urine analysis, micturition diary (MD) and urodynamic study (UDS). A percentage of 80% was assumed as highly sensitive and a diagnostic difference among tests of 10% would be considered clinically relevant. Tests' sensitivity for diagnosis of OAB was statistically established by two ways: isolated and combined. Besides, the direct and indirect costs of these tests performance were conducted. Cost-effectiveness study of clinical history (CH), MD and US for the diagnosis of OAB was performed. RESULTS: Overall sensitivity for OAB diagnosis is low for the 3 tests used in isolated way, whilst the combination of any two tests shows good overall sensitivity. The combination of CH and MD has appeared as the most cost-effective alternative to OAB diagnosis. CONCLUSIONS: For OAB diagnosis, CH-DM combination shows the same sensitivity than the association of either of them with the UDS, but unlike to these, it shows the lowest cost.

Development of urologic de novo malignancies after renal transplantation.

OBJECTIVES: The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS: We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS: We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS: There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.

Epigenetic regulation of PRAME in acute myeloid leukemia is different compared to CD34+ cells from healthy donors: effect of 5-AZA treatment.

PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies. Several studies have associated high PRAME RNA levels with good prognosis in acute myeloid leukemia (AML). PRAME expression is regulated at the epigenetic level. For this reason inhibitors of DNA methylation, such as 5-azacytidine, can modulate the expression of this TAAs. In the current study we analyzed the effect of 5-azaC on the expression of PRAME in blasts versus CD34+ cells from healthy donors in an attempt to increase its expression, thus inducing a potential target for therapeutic strategies.

Donor age and degree of HLA matching have a major impact on the outcome of unrelated donor haematopoietic cell transplantation for chronic myeloid leukaemia.

We analysed the outcome of 92 consecutive unrelated donor haematopoietic cell transplantations (UD-HCTs) performed in Spain to treat adult patients with CML in the first chronic phase (1CP). Patients' and donors' median age was 32 (15-49) and 36 (22-56) years, respectively. In all, 73 pairs (79%) matched for A, B+/-C and DRB1+/-DQB1 loci and 19 had > or =1 mismatch. Their probability of survival and disease-free survival at 4 years were 50 and 46%, respectively. Pretransplant factors associated with a better survival were patient age <25 years (P=0.035), donor age < or =36 years (P=0.012), use of cyclosporine since day -7 (P=0.001), and matching 8/8, 9/10 or 10/10 loci at allele level (P=0.003). In multivariate analysis only donor age (P=0.003; RR=3.1 (95% CI: 1.3-7.1)) and degree of HLA-matching (P=0.009; RR: 7.7 (95% CI: 1.8-33)) maintained their significance. The addition of these two variables to the EBMT prognostic score allowed an adequate risk assessment for patients receiving a UD-HCT during 1CP. Our analysis shows that in patients with a young and fully allele-matched donor, UD-HCT should be considered in the initial therapeutic algorithm due to its excellent outcome (92% survival at 2 years).

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético).

In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.

Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation.

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.

Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation.

Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow an early intervention in the event of low tumor burden, for which immunotherapy is highly effective. Some authors have found an association between persistence of MRD, mixed chimerism and risk of relapse. Nevertheless, data from the literature remain contradictory and further correlations should be established, especially in RIC transplants. In this study we have analyzed the impact of MRD and chimerism monitoring on the outcome of 34 patients undergoing RIC allogeneic SCT who were considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions. At day +100 25 (75%) patients reached complete remission (CR), there were five (15%) partial responses and three patients progressed. Incidence of grade 2-4 aGVHD and extensive cGVHD were 35% and 58%, respectively. Sixteen percent of patients developing aGVHD relapsed as compared to 47% in those without aGVHD (P = 0.03) and also 10% of patients developing cGVHD relapsed as compared to 50% relapses in those without cGHVD (P = 0.03). Four patients (12%) died due to early (n = 1) and late (n = 3) transplant-related mortality. After a median follow-up of 15 months, 24 out of the 34 patients remain alive. Projected overall survival and disease-free survival at 3 years are 68% and 63%, respectively. Early chimerism analysis showed 67% of patients with complete chimerism (CC) in bone marrow (BM), 86% in peripheral blood (PB), 89% in granulocytes and 68% in T lymphocytes. On day +100, these figures were 68%, 79%, 90% and 73%, respectively, and on day +180 there were 83% patients with CC in BM, 100% in PB, 100% in granulocytes and 100% in T lymphocytes. We observed a trend to a higher incidence of relapse in patients with mixed chimerism (MC) as compared to patients with CC. MRD monitoring by flow cytometry and/or RT-PCR analysis was performed in 23 patients. MRD assessment on days +21 to +56 after transplant allowed identification of patients at risk of relapse. In this sense, seven out of 12 patients (58.3%) who had positive MRD on days +21 to +56 relapsed as compared to none out of 11 patients who had negative MRD (P = 0.002). Of the seven patients with criteria to monitor MRD who relapsed after transplant, all but one remained MRD positive until relapse. By contrast, 10 patients remained MRD negative and all of them are in continuous CR. In nine additional patients, persistence of MRD or mixed chimerism was observed after transplant and withdrawal of cyclosporin with or without DLI was performed. Only two out of these nine patients relapsed. MRD clearance was preceded by CC and GVHD. In conclusion, in our study we found that RIC allogeneic transplantation can be used in patients considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions with both low toxicity and low transplant-related mortality. Simultaneous studies of both chimerism and MRD are a useful tool in order to predict risk of relapse in patients undergoing RIC transplants and so can be helpful for individualizing treatment strategies after transplant.

Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification.

Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10(-4) cells), and none have relapsed thus far; 37 were at low risk (10(-4) to 10(-3) cells); and 64 were at intermediate risk (fewer than 10(-3) to 10(-2) cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P =.0001). MRD level not only influences relapse-free survival but also overall survival (P =.003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML.

Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Mucormicosis diseminada en una paciente con leucemia mieloblástica aguda / Disseminated mucormycosis in a patient with acute myelogenous leukemia

Una paciente de 63 años afecta de leucemia aguda mieloblástica, tras 5 días de infección de las vías respiratorias altas, presentó una placa necrótica en ala nasal derecha; posteriormente, una lesión satélite en la pierna derecha y empeoramiento del estado general. Se aisló Mucor spp. En el cultivo de una de las dos biopsias efectuadas. En ambas había trombos formados por hifas no septadas. A pesar de un tratamiento precoz con anfotericina B intravenosa y desbridamiento quirúrgico la paciente falleció. La mucormicosis es una infección por hongos saprófitos de la clase de los zigomicetos que afecta a pacientes inmunodeprimidos. Las manifestaciones cutáneas en la mucormicosis diseminada son raras; sus formas de presentación varían: nódulos con centros equimóticos, placas eritematosas con centro purpúrico y lesiones similares al ectima gangrenoso. Dada su ubicuidad, para su diagnóstico se necesitan criterios microbiológicos e histopatológicos estrictos. El tratamiento más eficaz es el empleo de anfotericina B intravenosa a dosis altas y el desbridamiento quirúrgico, a pesar de lo cual la mortalidad es elevada (AU)

Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia.

We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day +21; bone marrow showed mixed chimaerism from day +21 to day +221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.

Allogeneic peripheral blood cell transplantation for hypereosinophilic syndrome with myelofibrosis.

Patients with hypereosinophilic syndrome (HES) display a very heterogeneous clinical picture ranging from asymptomatic cases to very aggressive forms. We report a 38-year-old woman with progressive HES who developed severe myelofibrosis and was treated by allogeneic stem cell transplantation, using peripheral blood (PBSCT) instead of bone marrow as the source of progenitor cells, after conditioning with cytoxan and busulphan. To the best of our knowledge, this is the first case of HES with myelofibrosis treated with PBSCT. The patient remains alive 8 months post-PBSCT, and bone marrow fibrosis has significantly decreased following transplantation. Bone Marrow Transplantation (2000) 25, 217-218.