RESUMEN
PURPOSE: Mouse monoclonal antibody (mAb) M195 (anti-CD33) is reactive with most myeloid leukemia cells, monocytes, and hematopoietic progenitors, but not with other hematopoietic cells or stem cells nor with nonhematopoietic human tissues. A therapeutic dose-escalation study of M195 labeled with iodine 131 was conducted in patients with relapsed or refractory myeloid leukemias. METHODS: Twenty-four patients (16 relapsed or refractory acute myeloid leukemias, five blastic myelodysplastic syndromes [MDS], two chemotherapy-related secondary leukemias, and one blastic chronic myelogenous leukemia [CML]), including seven who had failed to respond to prior bone marrow transplantation (BMT), received from 50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. RESULTS: In 22 patients, whole-body gamma-imaging demonstrated marked uptake of antibody into all areas of bone marrow. Twenty-three patients (96%) demonstrated decreases in peripheral-blood cell counts, with decreased percentage of bone marrow blasts seen in 83% of cases. Eighty-nine percent of bone marrow biopsies examined quantitatively demonstrated substantial decreases in the number of blasts, with greater than 99% of blasts killed in some patients. The two cases that failed to demonstrate leukemic cytoreduction occurred in the first two dose levels. For 131I doses of 135 mCi/m2 or greater, pancytopenia was profound and lasted for at least 12 days. Eight patients had sufficient marrow cytoreduction to proceed to BMT. Three of these achieved marrow remission, one of 6+, and one of 9 months' duration. Two patients in blastic phase temporarily reverted to their original myelodysplastic states. Thirty-seven percent of assessable patients developed human anti-mouse antibody (HAMA). In two patients with HAMA who were re-treated, plasma 131I-M195 levels could not be maintained and no therapeutic effect resulted. Significant nonhematologic toxicity (hepatic) was seen in one patient and the maximum-tolerated dose (MTD) was not reached. CONCLUSION: These data suggest that safe leukemic cytoreduction can be achieved with 131I-M195 even in multiply relapsed or chemotherapy-refractory leukemias. This agent may be useful as part of a preparative regimen for BMT.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Radioisótopos de Yodo/uso terapéutico , Leucemia Mieloide/radioterapia , Radioinmunoterapia , Adolescente , Adulto , Anciano , Animales , Médula Ósea/efectos de la radiación , Niño , Preescolar , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Radioinmunoterapia/efectos adversos , Recurrencia , Resultado del TratamientoRESUMEN
Ten patients with myeloid leukemias were treated in a phase I trial with escalating doses of mouse monoclonal antibody (mAb) M195, reactive with CD33, a glycoprotein found on myeloid leukemia blasts and early hematopoietic progenitor cells but not on normal stem cells. M195 was trace-labeled with iodine-131 (131I) to allow detailed pharmacokinetic and dosimetric studies by serial sampling of blood and bone marrow and whole-body gamma-camera imaging. Total doses up to 76 mg were administered safely without immediate adverse effects. Absorption of M195 onto targets in vivo was demonstrated by biopsy, pharmacology, flow cytometry, and imaging; saturation of available sites occurred at doses greater than or equal to 5 mg/m2. The entire bone marrow was specifically and clearly imaged beginning within hours after injection; optimal imaging occurred at the lowest dose. Bone marrow biopsies demonstrated significant dose-related uptake of M195 as early as 1 hour after infusion in all patients, with the majority of the dose found in the marrow. Tumor regressions were not observed. An estimated 0.33 to 1.0 rad/mCi 131I was delivered to the whole body, 1.1 to 6.1 rad/mCi was delivered to the plasma, and up to 34 rad/mCi was delivered to the red marrow compartment. 131I-M195 was rapidly modulated, with a majority of the bound immunoglobulin G (IgG) being internalized into target cells in vivo. These data indicate that whole bone marrow ablative doses of 131I-M195 can be expected. The rapid, specific, and quantitative delivery to the bone marrow and the efficient internalization of M195 into target cells in vivo also suggest that the delivery of other isotopes such as auger or alpha emitters, toxins, or other biologically important molecules into either leukemia cells or normal hematopoietic progenitor cells may be feasible.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Médula Ósea/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/farmacocinética , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Médula Ósea/diagnóstico por imagen , Evaluación de Medicamentos , Femenino , Citometría de Flujo , Semivida , Humanos , Infusiones Intravenosas , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , CintigrafíaRESUMEN
Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9-acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA-containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Amsacrina/uso terapéutico , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Femenino , Hemorragia/etiología , Hemorragia/mortalidad , Heparina/efectos adversos , Humanos , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso/complicaciones , Pronóstico , Inducción de Remisión , Tioguanina/uso terapéuticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Evaluación de Medicamentos , Humanos , Idarrubicina/administración & dosificaciónRESUMEN
We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Citarabina/administración & dosificación , Citarabina/farmacocinética , Evaluación de Medicamentos , Femenino , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/farmacocinética , Masculino , Persona de Mediana EdadRESUMEN
Twenty-three of 26 patients with hairy cell leukemia evaluable for response to splenectomy had significant improvement in anemia, thrombocytopenia, and/or neutropenia. Eight of the 23 had a recurrence of cytopenia after a median response duration of 4 to 5 months (range, 1-22). The remaining 15 patients did not have a recurrence of cytopenia at 20 months median follow-up (range, 1-76). Six patients with postsplenectomy cytopenia were given androgenic steroids. Two of the six had an improvement in anemia and thrombocytopenia, and a third patient had an improvement in neutropenia. It was concluded that, although most patients with hairy cell leukemia have initial improvement in cytopenia with splenectomy, a significant number of them either fail to respond or have recurrent cytopenia after initial response to splenectomy. A trial of androgenic steroids is a reasonable therapeutic option in these patients. Alternative therapies are reviewed and recommendations made.
Asunto(s)
Anabolizantes/uso terapéutico , Leucemia de Células Pilosas/terapia , Esplenectomía , Adulto , Anciano , Femenino , Fluoximesterona/uso terapéutico , Hemoglobinas/análisis , Humanos , Leucemia de Células Pilosas/sangre , Leucemia de Células Pilosas/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Oximetolona/uso terapéutico , Recuento de Plaquetas , RecurrenciaRESUMEN
Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.
Asunto(s)
Alcaloides/uso terapéutico , Antineoplásicos , Harringtoninas/uso terapéutico , Leucemia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Médula Ósea/efectos de los fármacos , Trasplante de Médula Ósea , Evaluación de Medicamentos , Harringtoninas/efectos adversos , Homoharringtonina , Humanos , Hiperglucemia/inducido químicamente , Hipotensión/inducido químicamente , Infusiones Parenterales , Recuento de Leucocitos , Persona de Mediana Edad , Recuento de PlaquetasRESUMEN
Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.
Asunto(s)
Antineoplásicos/uso terapéutico , Daunorrubicina/análogos & derivados , Leucemia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Daunorrubicina/efectos adversos , Daunorrubicina/metabolismo , Daunorrubicina/uso terapéutico , Evaluación de Medicamentos , Femenino , Humanos , Idarrubicina , Cinética , Masculino , Persona de Mediana EdadRESUMEN
We performed cytogenetic analyses using banding techniques on 89 adults with acute nonlymphoblastic leukemia prior to receiving protocol chemotherapy. The relationships of cytogenetic findings both to outcome and to other pretreatment variables (particularly the presence or absence of Auer rods) were analyzed. Patients were followed up to 90+ months. When patients were grouped according to cytogenetic findings (NN: all normal metaphases; AA: all abnormal metaphases; AN: both normal and abnormal metaphases; F: no evaluable metaphases; I: insufficient (less than three) metaphases) no significant differences were noted with regard to age, sex, terminal transferase positivity, complete remission rate, remission duration or survival. The marrow aspirates of patients with only normal (69%) metaphases or no evaluable metaphases (64%) were more likely to display Auer rods than specimens from individuals with only abnormal (26%) or a mixture of normal and abnormal (42%) metaphases (p = 0.03). The presence of Auer rods in the pretreatment marrow aspirate was associated with an increased complete remission rate (71% vs 41%, p = 0.004), median remission duration (12 months vs 9 months, p = 0.02), and median survival (13 months vs 4 months, p = 0.01). Using multivariable analyses, the presence or absence of Auer rods was the pretreatment factor that most significantly predicted response and survival in this group of patients. The presence of a normal karyotype in the initial cytogenetic preparation is associated with the presence of Auer rods. The finding of Auer rods in the initial bone marrow predicts greater response and longer survival in acute nonlymphoblastic leukemia.
Asunto(s)
Aberraciones Cromosómicas , Leucemia/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Cariotipificación , Leucemia/mortalidad , Leucemia/patología , Masculino , Metafase , Persona de Mediana EdadRESUMEN
We investigated the incidence of leukemia occurring subsequent to the treatment of germ cell tumors in men at our institution over a 30-year interval and found four patients with acute nonlymphocytic leukemia (ANLL) and one patient with chronic myelomonocytic leukemia. The relative risk (observed/expected cases) estimates for the development of leukemia ranged from 13.7 (P = .0005) in the total population to 50.1 (P = .0001) in the group treated with cytotoxic agents alone. All three patients with ANLL treated with contemporary antileukemic therapy had complete responses, with survivals of 7, 29, and 133 + months. In a review of the literature, 14 additional cases of germ cell tumors were found in which the men subsequently developed leukemia. It is concluded that leukemia following germ cell tumors is increased in incidence and is likely to be treatment induced. Complete responses and long-term survival are possible in secondary leukemia and aggressive antileukemic therapy should be given.
Asunto(s)
Leucemia/etiología , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Testiculares/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Disgerminoma/tratamiento farmacológico , Disgerminoma/radioterapia , Humanos , Leucemia/inducido químicamente , Leucemia Eritroblástica Aguda/etiología , Leucemia Monocítica Aguda/etiología , Leucemia Mieloide/inducido químicamente , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Inducida por Radiación/etiología , Masculino , Riesgo , Teratoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/radioterapia , Factores de TiempoRESUMEN
Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfoide/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two of these patients have relapsed while receiving maintenance chemotherapy; one died 1 mo after achieving remission due to the occurrence of cholycystitis in the setting of pancytopenia and one patient underwent bone marrow transplantation and is in remission at 8 mo after the second remission. Both patients who failed primary induction therapy remain in remission at 11 and 36 mo, respectively. The use of AMSA should be considered for patients with ALL who fail primary induction as well as those whose leukemia becomes resistant to conventional agents.
Asunto(s)
Aminoacridinas/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia Linfoide/tratamiento farmacológico , Adolescente , Adulto , Amsacrina , Antineoplásicos/administración & dosificación , Femenino , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Seventy-nine adult patients with acute nonlymphoblastic leukemia (ANLL) were treated on the L-6 protocol at Memorial Sloan-Kettering Cancer Center between May 1970 and January 1974. Forty-two patients achieved a complete remission (CR) and nine of these are still disease free, with a minimum of seven years of follow-up. An extensive statistical analysis has been carried out on a large number of pretreatment and treatment characteristics to identify factors related to CR and remission duration. Multivariate regression techniques yielded as favorable characteristics associated with CR, in order of importance: young age at diagnosis, the presence of Auer rods at diagnosis, and treatment with Pseudomonas vaccine. A regression model for remission duration identified as favorable prognostic factors for long-term remission: at most two courses of induction therapy, an intermediate age range, and a low platelet count at diagnosis.
Asunto(s)
Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Vacunas Bacterianas/uso terapéutico , Carmustina/administración & dosificación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/administración & dosificación , Leucemia/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Pseudomonas/inmunología , Estadística como Asunto , Tioguanina/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Alcalosis Respiratoria/diagnóstico , Candidiasis/diagnóstico , Hepatitis/diagnóstico , Leucemia/complicaciones , Dolor/diagnóstico , Abdomen , Enfermedad Aguda , Adulto , Anciano , Candidiasis/complicaciones , Femenino , Granuloma/diagnóstico , Granuloma/etiología , Humanos , Remisión EspontáneaRESUMEN
We treated 13 adult patients with acute leukemia or chronic myelocytic leukemia (CML) in blast phase using succinylated Acinetobacter glutaminase-asparaginase (SAGA) administered on a daily dose schedule. SAGA reduced the peripheral blast count in two patients with acute lymphoblastic leukemia and two with blastic CML; however, no patient achieved either complete or partial remission. Marked central nervous system toxic effects (encephalopathy and coma) were observed, limiting treatment in patients whose disease appeared responsive; this effect finally prompted early discontinuance of the trial. Other toxic effects observed included nausea, hyperglycemia, and respiratory alkalosis. Hypersensitivity reactions to the enzyme were not seen. Pharmacologic analyses showed that prolonged blood glutamine depletion was achieved only by daily enzyme administration; however, we noted the importance of performing amino acid analysis on blood which was deproteinized immediately following phlebotomy. Our results demonstrate excessive central nervous system toxicity when glutaminase-asparaginase is administered on a daily schedule. Because of this effect, we propose that future trials of similar enzymes be limited to short courses of enzyme therapy, possibly with the addition of antimetabolites or amino acid analogs, which could enhance the antitumor effect without increasing toxicity.
Asunto(s)
Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Glutaminasa/uso terapéutico , Leucemia Linfoide/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide/tratamiento farmacológico , Leucemia/tratamiento farmacológico , Acinetobacter/enzimología , Adulto , Asparaginasa/administración & dosificación , Ensayos Clínicos como Asunto , Esquema de Medicación , Estudios de Seguimiento , Glutaminasa/administración & dosificación , HumanosRESUMEN
Fifty-one adult patients with acute nonlymphocytic leukemia (excluding acute promyelocytic leukemia) were treated on the L-12 protocol. The L-12 differed from the preceding L-6 in that 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine (AAFC), replaced arabinosylcytosine (ara-C) together with 6-thioguanine (TG) for remission induction. Achievement of remission was followed by an extended 14-week multi-drug consolidation program. With this more intense regimen, an overall complete remission rate of 49% and a median remission duration of 23.7 months were achieved; these results were not significantly better than the 57% complete remission rate and 8.6 months median remission duration obtained with the L-6 regimen. Four year disease-free survival was 22% on the L-12 compared with 16% on the L-6 protocol. No relationship between prognosis and FAB classification was found on either the L-6 or the L-12 protocol.
Asunto(s)
Ancitabina/análogos & derivados , Antineoplásicos/administración & dosificación , Citarabina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia/tratamiento farmacológico , Tioguanina/administración & dosificación , Adolescente , Adulto , Anciano , Ancitabina/administración & dosificación , Ancitabina/efectos adversos , Antineoplásicos/efectos adversos , Vacunas Bacterianas/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Leucemia/patología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Pseudomonas aeruginosa , Distribución Aleatoria , Tioguanina/efectos adversosRESUMEN
One-hundred-one adult patients with ALL were analyzed to determine the prognostic implications of splenomegaly occurring at any time during the course of their illness. The clinical status of the spleen at presentation was not found to be of major prognostic significance. Complete response rates, remission durations, and survivals did not differ between patients with and without splenomegaly at presentation. An enlarged spleen accompanied relapse in four patients. In six additional patients, splenomegaly was present during complete remission, and splenectomies performed in five of these patients revealed no evidence of leukemia to account for the splenomegaly. Splenectomy does not appear to be detrimental, as all five patients are currently in complete remission from 20 to 63 mo after splenectomy. Evidence implicating the spleen as a source of an antibody directed against autologous leukemia cells in one patient is reviewed.
Asunto(s)
Leucemia Linfoide/complicaciones , Esplenomegalia/complicaciones , Adolescente , Adulto , Anciano , Médula Ósea/patología , Femenino , Humanos , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/mortalidad , Masculino , Persona de Mediana Edad , Esplenectomía , Esplenomegalia/diagnóstico , Esplenomegalia/mortalidadRESUMEN
Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.