Individualizing oral busulfan dose after using a test dose in patients undergoing hematopoietic stem cell transplantation: pharmacokinetic characterization.

BACKGROUND: Busulfan is an alkylating agent used for conditioning patients undergoing hematopoietic stem cell transplantation with a narrow therapeutic range and highly variable pharmacokinetics. High concentrations induce toxicity, especially hepatic veno-occlusive disease, also referred to as sinusoidal obstruction syndrome. This study aimed to assess busulfan pharmacokinetic variability in pretransplant conditioning regimens using an analytical method validated by high-performance liquid chromatography coupled to diode array detector (HPLC/PDA). METHODS: Eight patients who used the test dose (TD) of 1 mg/kg busulfan 10 days before conditioning were included, and 10 serial blood samples were collected to determine: the elimination half-life (t1/2), total area under the curve (AUCT), total clearance (Cl(T)/F), and plasma concentration at steady state (C(ss)), using a monocompartmental model and first-order kinetics. The instrumental conditions were: HPLC/PDA Shimadzu, column ACE C18 (150 mm × 4 mm); methanol/water/acetonitrile (65:20:15) eluent flow rate of 1 mL/min; 1,6-bis-(methanesulfonyloxy)-hexane; UV λ = 276 nm; analysis time 17 minutes; and derivatization with sodium diethylcarbamate. The dose was adjusted, and 4 blood samples per day were collected at days 2, 3, and 4 of treatment for new plasma determinations. RESULTS: Four patients needed higher doses; the mean dose administered was 1.02 ± 0.19 mg/kg. Mean results at TD: t1/2 = 2.88 ± 0.5 hours; Cl(T)/F = 0.18 ± 0.03 L · h(-1) · kg(-1); AUC(T) = 5461.00 ± 961.15 ng · mL(-1) · h(-1); and C(ss) = 911.3 ± 159.8 ng/mL. Mean results of samples collected during conditioning: t1/2 = 3.21 ± 0.9 hours; Cl(T)/F = 0.13 ± 0.02 L · h(-1) · kg(-1); AUC(T) = 7571 ± 1705 ng · mL(-1) · h(-1); and C(ss) = 1262.0 ± 284.3 ng/mL. CONCLUSIONS: High variability in the assessed pharmacokinetic parameters was observed, with a 38% variation in C(ss) between TD and conditioning regimen; Cl(T)/F decreased by 30%, suggesting drug accumulation after multiple-dose regimen. Although being lower than reported in the literature, this variation may be associated with toxicity of the proposed treatment, justifying patient monitoring and enhancing validity of previous pharmacokinetic evaluation using TD regimen.

Effect of low-level laser therapy on inflammatory mediator release during chemotherapy-induced oral mucositis: a randomized preliminary study.

Patients undergoing hematopoietic stem cell transplantation (HSCT) are submitted to a conditioning regimen of high-dose chemotherapy, with or without radiation therapy, which usually results in oral ulcerations and mucosal barrier breakdown. Oral mucositis (OM) is a common and debilitating toxicity side effect of autologous and allogeneic HSCT. The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) on the severity of OM and inflammatory mediator (TNF-α, IL-6, IL-1ß, IL-10, TGF-ß, metalloproteinases, and growth factors) levels in saliva and blood of HSCT patients. Thirty patients were randomly assigned to two groups: control (n = 15) and laser (n = 15). LLLT was applied from the first day of the conditioning regimen until day 7 post-HSCT (D + 7). Saliva and blood were collected from patients on admission (AD), D-1, D + 3, D + 7, and on marrow engraftment day (ME). Clinical results showed less severe OM in the laser group (p < 0.05). The LLLT group showed increased matrix metalloproteinase 2 (MMP-2) levels in saliva on D + 7 (p = 0.04). Significant differences were also observed for IL-10 on D + 7 and on ME in blood plasma, when compared to the control group (p < 0.05). No significant differences were seen in saliva or blood for the other inflammatory mediators investigated. LLLT was clinically effective in reducing the severity of chemotherapy-induced OM in HSCT patients, and its mechanism of action does not seem to be completely linked to the modulation of pro- or anti-inflammatory cytokines, growth factors or matrix metalloproteinases.

Transplante autólogo de células-tronco em linfoma de Hodgkin: análise de uma opção terapêutica / Autologous stem-cell transplantation in Hodgkin's lymphoma: analysis of a therapeutic option

Objective: To report the clinical progress of patients with Hodgkin’slymphoma treated with autologous transplantation after failure or relapse of first-line treatment with chemotherapy and/or radiation therapy. Methods: The results of a retrospective analysis of 31 patients submitted to autologous transplantation as second-line treatment, between April 2000 and December 2008, were analyzed. Fourteen men and seventeen women, with a median age of 27 years, were submitted to autologous transplantation for relapsed (n = 21)or refractory (n = 10) Hodgkin’s lymphoma. Results: Mortality related to treatment in the first 100 days after transplant was 3.2%. With a mean follow-up period of 18 months (range: 1 to 88 months), the probability of global survival and progression-free survival in 18 months was 84 and 80%, respectively. The probability of global survival and progression-free survival at 18 months for patients withchemosensitive relapses (n = 21) was 95 and 90%, respectively, versus 60 and 45% for patients with relapses resistant to chemotherapy(n = 10) (p = 0.001 for global survival; p = 0.003 for progressionfreesurvival). In the multivariate analysis, absence of disease or pretransplantdisease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85) and progression-free survival(p= 0.01; RR: 0.040; 95%CI: 0.007-0.78). Conclusion: Autologoustransplantation of stem-cells is a therapeutic option for Hodgkin’slymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

Objetivo: Relatar a evolução dos pacientes com linfoma de Hodgkintratados com transplante autólogo após falha ou recidiva do tratamentode primeira escolha com quimioterapia e/ou radioterapia. Métodos: Foram analisados os resultados de uma análise retrospectiva em 31 pacientes submetidos a transplante autólogo como terapia de segunda escolha, entre Abril de 2000 e Dezembro de 2008. Quatorzehomens e dezessete mulheres, com idade mediana de 27 anos, foram submetidos a transplante autólogo por linfoma de Hodgkin após recidiva (n = 21) ou por refratariedade (n = 10). Resultados: A mortalidade relacionada ao tratamento nos primeiros 100 dias pós transplante foi de 3,2%. Com um acompanhamento médio de 18 meses(variação: 1 a 88), a probabilidade de sobrevida global e sobrevida livre de progressão em 18 meses foi de 84 e 80%, respectivamente. A probabilidade de sobrevida global e sobrevida livre de progressão aos 18 meses para pacientes com recidivas quimiossensíveis (n = 21) foi de 95 e 90%, respectivamente, versus 60 e 45% para os pacientes com recidiva resistente à quimioterapia (n = 10) (p = 0,001 para sobrevida global; p = 0,003 para sobrevida livre de progressão). Na análise multivariada, a ausência de doença ou doença pré-transplante < 5 cm foi um fator favorável para a sobrevida global (p= 0,02; RR: 0,072; IC95%: 0,01-0,85) e sobrevida livre de progressão (p= 0,01;RR: 0,040; IC95%: 0,007-0,78). Conclusão: O transplante autólogode células-tronco constitui uma opção terapêutica para pacientes com linfoma de Hodgkin após uma primeira recaída. Resultados promissores foram observados em pacientes com baixa carga tumoral ao transplante.

The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial.

BACKGROUND DATA AND OBJECTIVE: Patients who have received high doses of chemotherapy, either alone or in combination with total body irradiation often cite oral mucositis (OM) as the most debilitating side effect. The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) on the prevention of conditioning-induced OM in hematopoietic stem cell transplantation (HSCT). METHODS: We randomized 42 patients who underwent autologous or allogeneic HSCT. A low-level InGaAlP diode laser was used, emitting light at 660 nm, 40 mW, and 4 J/cm(2). An evaluation of OM was carried out using the World Health Organization scale. RESULTS AND CONCLUSION: In the LLLT group, 57.1% of patients had an OM grade 0, 9.6% had grade 1, and 33.3% had grade 2, whereas in the control group, only 4.8% of patients were free of OM (grade 0). Our results indicate that the preventive use of LLLT in patients who have undergone HSCT is a powerful instrument in reducing OM incidence.

Autologous stem-cell transplantation in Hodgkin's lymphoma: analysis of a therapeutic option.

OBJECTIVE: To report the clinical progress of patients with Hodgkin's lymphoma treated with autologous transplantation after failure or relapse of first-line treatment with chemotherapy and/or radiation therapy. METHODS: The results of a retrospective analysis of 31 patients submitted to autologous transplantation as second-line treatment, between April 2000 and December 2008, were analyzed. Fourteen men and seventeen women, with a median age of 27 years, were submitted to autologous transplantation for relapsed (n = 21) or refractory (n = 10) Hodgkin's lymphoma. RESULTS: Mortality related to treatment in the first 100 days after transplant was 3.2%. With a mean follow-up period of 18 months (range: 1 to 88 months), the probability of global survival and progression-free survival in 18 months was 84 and 80%, respectively. The probability of global survival and progression-free survival at 18 months for patients with chemosensitive relapses (n = 21) was 95 and 90%, respectively, versus 60 and 45% for patients with relapses resistant to chemotherapy (n = 10) (p = 0.001 for global survival; p = 0.003 for progression-free survival). In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85) and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78). CONCLUSION: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin's lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

O papel do laser de baixa intensidade e da cloredidina 0, 12% no tratamento da mucosite bucal em crianças leucêmicas submetidas à quimioterapia / The utilization of the low energy laser and chlorexidine 0, 12% in the management of oral mucositis due to chemotherapy unn children with leukemia

No tratamento das leucemias é utilizada a quimioterapia, que apresenta vários efeitos colaterais. A mucosite bucal é a principal causa de dor durante a quimioterapia e a complicação mais comum dotratamento para neoplasias hematológicas. Esse estudo teve o objetivo de avaliar o uso do laser debaixa intensidade e da clorexidina 0,12% no tratamento da mucosite bucal decorrente de quimioterapiaem crianças leucêmicas. A amostra foi constituída por 10 crianças (Grupo Experimental) com leucemia aguda submetidas à quimioterapia e portadoras de mucosite bucal Graus I, II ou III, atendidas noHospital Araújo Jorge da Associação de Combate ao Câncer em Goiás. Também fazia parte da amostra, dados de 24 prontuários de pacientes infantis com leucemia aguda, tratados no mesmo hospital, que apresentaram mucosite bucal como intercorrência do tratamento de quimioterapia. Os pacientes do Grupo Experimental foram aleatoriamente distribuídos para receber o tratamento 1 (clorexidina 0,12%) ou 2 (laser). A presença e o grau de mucosite eram avaliados pelo mesmo examinador. Para comparação, os dados de prontuários de pacientes previamente tratados foram registrados, sendo que para estes, era utilizado apenas o tratamento sintomático da mucosite bucal. Os registros, da mesma forma, eram anotados quanto à presença e grau de mucosite. A mucosite bucal foi menos freqüente e teve menor tempo de duração no grupo que recebeu tratamento (clorexidina ou laser) do que no gruposem tratamento. A associação das várias formas de tratamento (higiene bucal, clorexidina e laser) leva à redução do número de episódios de mucosite bem como menor duração das lesões

Chemotherapy, which presents several side effects, is used in the management of leukemia. Oral mucositis is the main cause of pain during chemotherapy and is the most common complication in the management of hematological cancer. The aim of the current study was to investigate the utilization of the low-energy laser and the use of chlorexidine 0,12% in the management of oral mucositis due to chemotherapy in children with leukemia. The study group was composed of 10 children with acute leukemia, who developed oral mucositis grade I, II, or III, and who underwent chemotherapy at the Araújo Jorge Hospital at the Combat Cancer Association of Goias. 24 case records of infant patients with acute leukemia, who were managed at the already mentioned hospital, and who developed oral mucositis as intercurrence of chemotherapy, were also included. The patients in the Study Group were randomized tobe treated with 1 (chlorexidine 0,12%) or 2 (laser). The presence and the degree of mucositis being evaluated by the same examiner. For comparison, data in the charts of patients previously treated were registered. For these patients, just the symptomatic treatment of the oral mucositis was used. The data about the presence and degree of mucositis were equally logged. Oral mucositis was less frequent and had a shorter period of duration in the treated group (chlorexidine or laser) than in the untreated group. The association of various forms of treatment (oral hygiene, chlorhexidine and laser) decreases the number of mucositis occurrences and shortens duration of the lesions

Clinical manifestations due to severe plasminogen deficiency: a case report.

Plasminogen deficiency is a rare, destructive, and badly defined disorder. Recurrent and progressive gingival nodular hyperplasia with ulceration would appear to be an unreported complication caused by this deficiency. In some of the reported cases, gingival hyperplasia occurred in association with an eye disease called ligneous conjunctivitis. Including this case report, only 11 patients with proven functional plasminogen and oral lesions have been reported in the literature in English. The purpose of this paper was to present the case of a child patient with recurrent clinical manifestations caused by severe plasminogen deficiency who responded positively to corticosteroid treatment.

Transfusäo intra-uterina intravascular: diagnóstico e conduta na isoimunizaçäo-Rh

A principal indicaçäo da cordocentese na terapêutica fetal é na correçäo da anemia fetal. Até recentemente, a transfusäo intraperitoneal foi o método usado no tratamento da anemia severa devido a isoimunizaçäo. Em dois pacientes com severa isoimunizaçäo foram realizadas transfusöes intra-uterinas intravasculares. Elas eram Rh (-) e sensibilizadas ao antígeno D. A primeira TIV foi realizada nas 21ª e 24ª semanas de gravidez,respectivamente. Das 10 TIU, nove foram TIV e uma TIP. Todas foram realizadas com a ajuda do ultra-som, e as complicaçöes apresentadas - bradicardia fetal, corioamnionite e metrossístoles - näo impediram o nascimento e sobrevida dos dois fetos. A análise desta experiência é apresentada, e os comentários mostraram que a TIV parece ser um método eficaz na terapêutica da eritroblastose fetal