RESUMO
Microangiopathic hemolytic anemia (MAHA) is a well-described complication of stem cell transplantation. Plasmapheresis is one modality utilized as therapy for patients who develop this complication. However, plasmapheresis may alter whole blood levels of certain medications and its effect on tacrolimus in bone marrow transplant patients is unknown. Because tacrolimus has a narrow therapeutic range, the effect of plasmapheresis on whole blood concentrations would be important to know. We report three allogeneic BMT patients who were receiving tacrolimus as acute GVHD therapy while undergoing plasmapheresis for MAHA. Tacrolimus levels seemed unaffected by plasmapheresis in these patients.
Assuntos
Anemia Hemolítica/etiologia , Anemia Hemolítica/prevenção & controle , Transplante de Medula Óssea/efeitos adversos , Imunossupressores/sangue , Plasmaferese , Tacrolimo/sangue , Adulto , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Lactente , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Transplante HomólogoRESUMO
High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m(2) plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D +100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL+AF+AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D +1163 (range D +824 to D +1630); one of these patients had a nonmyeloablative allograft as consolidation on D +106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL+AF+AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.
Assuntos
Amifostina/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Melfalan/administração & dosagem , Protetores contra Radiação/administração & dosagem , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
The feasibility of long-term storage of commonly used ophthalmic antimicrobial solutions was studied. Solutions of tobramycin 15 mg/mL (as the sulfate salt), cefazolin 33 mg/mL (as the sodium salt), and vancomycin 50 mg/mL (as the hydrochloride salt), each in artificial tears, were prepared with aseptic technique. Ten 15-mL portions of each solution were prepared; five of each were stored at 4 degrees C and the other five at 25 degrees C. Samples of each portion were tested before storage and 7, 14, 21, and 28 days after preparation for osmolality, pH, and antimicrobial activity. For the tobramycin solution there were no differences in osmolality or the zone of inhibition associated with temperature or time. The pH dropped between days 0 and 7 at both temperatures. For the cefazolin solution there were no differences in osmolality associated with temperature or time. The pH was higher in portions stored at 25 degrees C than at 4 degrees C and increased over time in portions stored at either temperature. The zone of inhibition was larger for portions stored at 4 degrees C than at 25 degrees C but did not change over time. For the vancomycin solution there were no differences in osmolality associated with temperature or time. The pH did not differ between portions stored at 4 and 25 degrees C but dropped sharply at both temperatures between days 0 and 7. The zone of inhibition did not differ with temperature or time. The tobramycin solution could be stored for 28 days at room temperature and the cefazolin solution for 28 days under refrigeration. The pH of the vancomycin solution changed too quickly for storage to be recommended.
Assuntos
Anti-Infecciosos/química , Soluções Oftálmicas/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Cefazolina/administração & dosagem , Cefazolina/química , Cefalosporinas/administração & dosagem , Cefalosporinas/química , Composição de Medicamentos , Armazenamento de Medicamentos , Tobramicina/administração & dosagem , Tobramicina/química , Vancomicina/administração & dosagem , Vancomicina/químicaRESUMO
This study was conducted to define a new maximum tolerated dose and the dose-limiting toxicity (DLT) of melphalan and autologous hematopoietic stem cell transplantation (AHSCT) when used with the cytoprotective agent amifostine. Fifty-eight patients with various types of malignancy who were ineligible for higher-priority AHSCT protocols were entered on a phase I study of escalating doses of melphalan beginning at 220 mg/m(2) and advancing by 20 mg/m(2) increments in planned cohorts of 4 to 8 patients until severe regimen-related toxicity (RRT) was encountered. In all patients, amifostine 740 mg/m(2) was given on 2 occasions before the first melphalan dose (ie, 24 hours before and again 15 minutes before). AHSCT was given 24 hours after the first melphalan dose. Melphalan was given in doses up to and including 300 mg/m(2). Hematologic depression was profound, although it was rapidly and equally reversible at all melphalan doses. Although mucosal RRT was substantial, it was not the DLT, and some patients given the highest melphalan doses (ie, 300 mg/m(2)) did not develop mucosal RRT. The DLT was not clearly defined. Cardiac toxicity in the form of atrial fibrillation occurred in 3 of 36 patients treated with melphalan doses >/=280 mg/m(2) and was deemed fatal in 1 patient given melphalan 300 mg/m(2). (Another patient with a known cardiomyopathy was given melphalan 220 mg/m(2) and died as a result of heart failure but did not have atrial fibrillation.) Another patient given melphalan 300 mg/m(2) died of hepatic necrosis. The maximum tolerated dose of melphalan in this setting was thus considered to be 280 mg/m(2), and 27 patients were given this dose without severe RRT. Moreover, 38 patients were evaluable for delayed toxicity related to RRT; none was noted. Tumor responses have been noted at all melphalan doses and in all diagnostic groups, and 21 patients are alive at median day +1121 (range, day +136 to day +1923), including 16 without evidence of disease progression at median day +1075 (range, day +509 to day +1638). Amifostine and AHSCT permit the safe use of melphalan 280 mg/m(2), an apparent increase over the dose of melphalan that can be safely administered with AHSCT but without amifostine. Further studies are needed not only to confirm these findings, but also to define the antitumor efficacy of this regimen. Finally, it may be possible to evaluate additional methods of further dose escalation of melphalan in this setting.