Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation.

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days -9 and -2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day -5 and tacrolimus (Tk) from -3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2-4 and 3-4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.

Potential protective effect of Helicobacter pylori on the development of gastrointestinal GvHD.

Previous reports ascribe a modulating capacity of the immune response to Helicobacter pylori (HP). Our hypothesis was to demonstrate in a prospective study that HP infection could have a protective effect against development of gastrointestinal GvHD in patients receiving allogeneic hematopoietic cell transplantation (HCT). Presence of HP before transplant was determined using C(13) urea breath test. Seventy-nine patients receiving an allogeneic HCT were included and 93.7% of them received PBSC; in 51.9%, the donor was unrelated. Acute gastrointestinal GvHD was diagnosed in 51.9% (n=41). In the multivariable analysis, HP infection was associated with a lower frequency of gastrointestinal GvHD (odds ratio (OR)=0.19 (95% confidence interval (CI): 0.05-0.67); in contrast, an unrelated donor was associated with a higher frequency of gastrointestinal GvHD (odds ratio=5.4 (95% confidence interval: 1.6-18.2). One year overall survival (OS) was 74%. In the multivariate Cox proportional-hazards regression analysis, stages 0-II gastrointestinal GvHD (hazards ratio (HR)=0.19), reduced intensity conditioning (HR=0.04) and tacrolimus-sirolimus GvHD prophylaxis (HR=0.06) were all associated with a better OS. In summary, HP infection could have a role in decreasing gastrointestinal GvHD in patients receiving allogeneic HCT from peripheral blood including related and unrelated donors.

Hemorrhagic cytitis after bone marrow transplantation.

OBJECTIVES: Hemorrhagic cystitis (HC) presenting with gross hematuria, bladder pain and urinary frequency develops in 13-38% of patients following bone marrow transplantation (BMT). The objective of the study was to study the characteristics of patients suffering hemorrhagic cystitis after hematopoietic stem cell transplantation in our center. METHODS: We conducted a retrospective chart review of all patients who underwent BMT at our institution between January 1996 and August 2012. We recorded the age, sex, diagnosis, conditioning regimen, interval between BMT and development of symptoms of cystitis and treatment instituted. RESULTS: Five hundred patients underwent BMT in the period of time studied. 52 of them developed hemorrhagic cystitis. The mean age of the affected patients was 39 years; there were 34 males and 18 females. The diagnoses include AML (n=11), ALL (n=8), CML (n=6), MDS (n=11), CLL (n=5), NHL (n=1), HD (n=5), MM (n=2), Medular aplasia((n=3). HC appeared 59.48 days after BMT. There were no differences between sexes. Mortality among the 52 patients was 51.14% but HC was not the cause of death in any patient. Polyomaviruses were detected in the urine of 78.94 % of survivors. CONCLUSIONS: Polyomavirus infection with BK and JC types is usually acquired in infancy and the virus remains latent in renal tissue. Immunosuppression facilitates reactivation of the renal infection and replication of the virus responsible for the clinical manifestations of HC. The differential diagnoses include other urinary infections, lithiasis, thrombocytopenia and adverse effects of pharmacological agents. The urologist plays a limited role in the management of this disease.

Cistitis hemorrágica en pacientes sometidos a trasplante de médula ósea / Hemorrhagic cytitis after bone marrow transplantation

OBJETIVOS: Tras trasplante alogénico de células hematopoyéticas aparece cistitis hemorrágica en 13-38% de casos, siendo los síntomas más frecuentes hematuria macroscópica con/sin coágulos, polaquiuria, dolor y espasmos vesicales. Estudiar las características de los pacientes que sufren cistitis hemorrágica tras trasplante de progenitores hematopoyéticos en nuestro centro. MÉTODOS: 500 pacientes recibieron trasplante alogénico de progenitores hematopoyéticos (TAPH) entre enero de 1996 y agosto de 2012, de los cuales 52 sufrieron cistitis hemorrágica. Investigamos edad, sexo, diagnóstico principal, régimen de acondicionamiento, tiempo desde TAPH hasta la cistitis, presencia de poliomavirus en orina, duración de la clínica, tratamiento recibido, supervivencia de los pacientes. RESULTADOS: Edad media 39 años (rango 19-66). 34 varones: 18 mujeres. Diagnóstico: LMA (n=11), LLA (n=8), LMC (n=6), SMD (n=11), LLC (n=5), LNH (n=1), EH (n=5), MM (n=2), Aplasia Medular (n=3). Cistitis hemorrágica a los 59,48 días post-trasplante, sin diferencia entre varones y mujeres. No hubo diferencias en el tipo de acondicionamiento administrado entre varones y mujeres. Se demostró la presencia en orina de Poliomavirus en 78,94% de los supervivientes. 8 pacientes requirieron evaluación por Urología durante el ingreso. Mortalidad de la muestra del 46,15%, ninguna muerte por la cistitis hemorrágica. CONCLUSIONES: La cistitis hemorrágica en pacientes sometidos a trasplante de médula ósea es una patología de alta prevalencia, apareciendo los poliomavirus BK y JC como virus emergentes en su etiología. Se ha de realizar un diagnóstico diferencial con infecciones urinarias de otro origen, causas farmacológicas, trombopenias secundarias a la enfermedad de base y litiasis urinarias. El urólogo participa poco en el manejo de esta patología

OBJECTIVES: Hemorrhagic cystitis (HC) presenting with gross hematuria, bladder pain and urinary frequency develops in 13-38% of patients following bone marrow transplantation (BMT). The objective of the study was to study the characteristics of patients suffering hemorrhagic cystitis after hematopoietic stem cell transplantation in our center. METHODS: We conducted a retrospective chart review of all patients who underwent BMT at our institution between January 1996 and August 2012. We recorded the age, sex, diagnosis, conditioning regimen, interval between BMT and development of symptoms of cystitis and treatment instituted. RESULTS: Five hundred patients underwent BMT in the period of time studied. 52 of them developed hemorrhagic cystitis. The mean age of the affected patients was 39 years; there were 34 males and 18 females. The diagnoses include AML (n=11), ALL (n=8), CML (n=6), MDS (n=11), CLL (n=5), NHL (n=1), HD (n=5), MM (n=2), Medular aplasia (n=3). HC appeared 59.48 days after BMT. There were no differences between sexes. Mortality among the 52 patients was 51.14 % but HC was not the cause of death in any patient. Polyomaviruses were detected in the urine of 78.94 % of survivors. CONCLUSIONS: Polyomavirus infection with BK and JC types is usually acquired in infancy and the virus remains latent in renal tissue. Immunosuppression facilitates reactivation of the renal infection and replication of the virus responsible for the clinical manifestations of HC. The differential diagnoses include other urinary infections, lithiasis, thrombocytopenia and adverse effects of pharmacological agents. The urologist plays a limited role in the management of this disease