RESUMO
Thirty-two months after the diagnosis and treatment of a T-lymphoblastic lymphoma with bone marrow involvement had been made in a 30-year-old patient, he developed fever up to 40 degrees C during maintenance treatment with methotrexate and 6-mercaptopurine. Later there were tender, blue-red skin eruptions, leukocytopenia (1.4 x 10(9)/l) and thrombocytopenia (29 x 10(9)/l). Histological examination of a skin biopsy revealed acute febrile neutrophilic dermatosis (Sweet's syndrome). Bone marrow biopsy revealed hyperplastic myelopoiesis. There was no evidence for acute myeloid leukaemia or lymphoma recurrence. After the maintenance treatment had been discontinued, treatment with methylprednisolone, 60 mg, was begun. The signs of Sweet's syndrome regressed, but thrombocytopenia and mild leukocytopenia remained. Six months later it was found by morphological and immunological tests that he had acute myeloid leukaemia without any chromosomal abnormalities. There was still no evidence for a recurrent T-lymphoblastic lymphoma.
Assuntos
Neutrófilos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Dermatopatias/complicações , Adulto , Humanos , Contagem de Leucócitos , Masculino , Pele/patologia , Trombocitopenia/complicaçõesRESUMO
In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Transplante de Medula Óssea , Terapia Combinada , Citarabina/administração & dosagem , Esquema de Medicação , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Prognóstico , Indução de RemissãoRESUMO
Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n = 44), autologous BM plus peripheral blood stem cells (PBSC) (n = 2), PBSC (n = 1), syngeneic (n = 1), or allogeneic BM (n = 3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n = 33) or resistant (n = 17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n = 44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n = 3). The patients receiving allogeneic transplants were treated with the CVB regimen (n = 2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61% +/- 9%, progression-free survival for patients with sensitive disease is 44% +/- 11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving > or = 600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.