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2.
Bone Marrow Transplant ; 51(10): 1337-1341, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27183094

RESUMO

Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m2 (Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) <60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ⩾60 mL/min (median 83 mL/min, range 60-128). Patients with CrCl <60 mL/min had longer time to neutrophil (P=0.008) and platelet engraftment (P<0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl <60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl <60 mL/min group and 47 months (range 1-45) in the CrCl ⩾60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P=0.0025). Multivariate analysis showed CrCl <60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min.


Assuntos
Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Insuficiência Renal/complicações , Adulto , Idoso , Creatinina/farmacocinética , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Melfalan/toxicidade , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Insuficiência Renal/mortalidade , Análise de Sobrevida
5.
Bone Marrow Transplant ; 46(10): 1326-30, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21132027

RESUMO

The assessment of a hematopoietic stem cell transplant (HSCT)-specific comorbidity index (HCT-CI) has been developed to predict the risk of TRM in patients undergoing allogeneic HSCT. As the myeloablative fludarabine/i.v. busulfan (FluBu4) regimen has been associated with limited extra-hematologic toxicity, we analyzed whether the HCT-CI represents a useful tool in transplant patients conditioned with this regimen. Of the 52 consecutive patients who received an allogeneic HSCT with FluBu4 at our institution, 50 were evaluable for assessing pre-transplant HCT-CI. Patients were divided into three groups: score 0 (n=7); score 1-2 (n=17) and score >3 (n=26). The three groups did not differ significantly in age, diagnosis, previous lines of chemotherapy and type of donor. High-risk disease was present in 57% of low, 82% of intermediate and 85% of high HCT-CI score groups (P=ns). Two-year TRM and OS was 14.3 and 85.7% in the low score group, 23.5 and 58.8% in the intermediate score group and 15.4 and 50% in the high HCT-CI score group (P=ns). In this study, the HCT-CI lacked sensitivity to reliably predict TRM although patients with no comorbidities showed a trend for improved survival.


Assuntos
Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Bussulfano/efeitos adversos , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do Tratamento , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico , Adulto Jovem
8.
Bone Marrow Transplant ; 45(2): 249-53, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19543331

RESUMO

A pretransplant test dose of i.v. BU was previously used in pediatric patients undergoing a reduced-intensity allogeneic hematopoietic SCT (HSCT). Here, we used a BU test dose in 23 adult patients who were not pancytopenic and underwent a myeloablative allogeneic HSCT prepared with fludarabine and i.v. BU (FluBU). Pharmacokinetics (PK) of BU were calculated after a test dose (0.8 mg/kg) was performed 2 weeks before transplant. Targeted BU area under the curve (AUC) range was 4800-5200 microM min. The mean BU dose calculated after the test dose was 3.5+/-0.5 mg/kg. To validate the test dose, PK studies were repeated in 17 patients after the first dose of BU during the conditioning regimen. An AUC below the therapeutic value of 4000 microM min was observed in 23% of the patients receiving a wt-based dose and in 0% of patients whose dose was calculated on the basis of the test dose (P=0.03). In patients who had a test dose, a significant correlation (P<0.0001) between the first and subsequent doses of BU during the conditioning regimen was observed. Our findings may allow more centers to pursue transplant strategies with targeted BU by overcoming the time limitation for PK studies during the conditioning regimen.


Assuntos
Bussulfano/farmacocinética , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adolescente , Adulto , Área Sob a Curva , Bussulfano/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Vidarabina/uso terapêutico
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