Autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas

O transplante autólogo de célula progenitora ou medula óssea (ATMO) tem demonstrado capacidade de superar resistência tumoral através da elevação da intensidade de dose de drogas disponíveis e radioterapia. ATMO foi inicialmente utilizado em LNH após recidiva em primeira linha ou refratários. ATMO tem demonstrado maior utilidade em condições clínicas mais favoráveis como na remissão parcial (RP), primeira remissão completa (RC) e como primeira linha após quimioterapia. Quimioterapia de alta dose e ATMO se tornaram a terapêutica standard para pacientes elegíveis com LNH agressivo, recorrente e quimiosensível. Pacientes primariamente refratários e com recidiva resistente não são boas indicações e devem ser considerados como grupo elegível para estudos de fase II. Talvez, haja um papel do ATMO em pacientes parcialmente responsivos. Entretanto, novos e grandes estudos randomizados são necessários para esclarecer esta questão. Um desafio para o manuseio dos linfomas é a definição da terapia de alta dose seguida do ATMO como terapêutica inicial para os LNH agressivos, identificando pacientes que não possam ser curados com terapêutica convencional. Uma série de estudos retrospectivos ou controlados parece indicar os chamados pacientes de "alto-risco", definido pela IPI como potencial alvo destas terapêuticas intensificadas. Entretanto, de acordo com dados publicados, o problema permanece aberto para debates. Estudos grandes e randomizados são necessários e bem vindos e devem ser considerados prioridade neste campo da ciência médica.

Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study.

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75.9 percent) affected by aggressive and 7 (24.1 percent) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.