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1.
Br J Haematol ; 204(4): 1288-1292, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38050458

RESUMEN

First-line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long-lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression-free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine.


Asunto(s)
Antineoplásicos , Leucemia de Células Pilosas , Humanos , Cladribina/uso terapéutico , Leucemia de Células Pilosas/patología , Médula Ósea/patología , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de Neoplasia , Factores Inmunológicos/uso terapéutico , Antimetabolitos/uso terapéutico , Antineoplásicos/uso terapéutico
2.
Hum Reprod ; 31(2): 263-72, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26705149

RESUMEN

STUDY QUESTION: Is spermatogenesis impairment caused by Hodgkin's lymphoma (HL) itself or by the various treatments? SUMMARY ANSWER: HL is not itself the main cause of impaired spermatogenesis, which is instead affected by the treatment; the extent of impairment depends on the type of treatment and the number of cycles. WHAT IS KNOWN ALREADY: Data in the literature are contradictory, although most studies found poor semen quality in HL patients prior to treatment. The impact of therapy on spermatogenesis depends on the type of treatment, but the time needed to recover testicular function following treatment with chemotherapeutic agents inducing azoospermia is unknown. STUDY DESIGN, SIZE, DURATION: In a retrospective study, the semen parameters of 519 patients (504 with sperm and 15 who were azoospermic) were investigated.HL patients were analysed before therapy. A longitudinal study was also conducted of semen quality in 202 patients pre- and post-ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) at T0 (baseline) and 6 (T6), 12 (T12) and 24 (T24) months after the end of treatment, and of 42 patients pre- and post-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), COPP/ABVD (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine and dacarbazine), OPP/ABVD (vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine and dacarbazine) or MOPP (mechlorethamine, vincristine, procarbazine and prednisone) and inguinal radiotherapy at different observation times (from T0 to 16 years after treatment). PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen parameters were examined according to World Health Organization 2010 criteria, evaluating sperm concentration, total sperm number, progressive motility and morphology. MAIN RESULTS AND THE ROLE OF CHANCE: Our data, which pertain to the largest caseload reported to date, indicate that 75% of HL patients are normozoospermic prior to treatment. The results from the HL patients studied pre- and post-therapy demonstrate that spermatogenesis recovery depends on the therapeutic regimen used. After ABVD, there was a statistically significant decrease in sperm concentration and total sperm number at T6 and T12 (P < 0.001; P < 0.01, respectively). There was a significant drop in progressive motility (P < 0.001) and a significant increase in abnormal forms (P < 0.01) at T6. The differences in sperm concentration, total sperm number and abnormal forms at T0 and T24 were not statistically significant, indicating that sperm quality had returned to pre-therapy values. The most interesting data in terms of patient management arise from the study of azoospermia induced by other chemotherapeutic agents. A high number of BEACOPP, COPP/ABVD, OPP/ABVD or MOPP cycles (≥6) induced a permanent absence of sperm in the seminal fluid, while even following a low number of cycles (<6), spermatogenesis only recovered after 3-5 years and semen quality was highly impaired. LIMITATIONS, REASONS FOR CAUTION: The study type (retrospective) and the low caseload and varying time of the follow-up do not permit any firm conclusions to be drawn about the recovery of spermatogenesis after BEACOPP or other combined therapies, or the identification of any risk factors for testicular function in treated patients. WIDER IMPLICATIONS OF THE FINDINGS: The pretreatment semen parameters of HL patients in this study were better than some results reported in the literature, with a higher percentage of normozoospermic patients. Strengths of this study were the large caseload of HL patients and a high degree of consistency in semen analysis, as all parameters were assessed in the same laboratory. Following the azoospermia induced by different chemotherapeutic protocols, spermatogenesis may take several years to recover. Awareness of this issue will enable oncologists to better inform patients about the possibility of recovering fertility post-treatment and also demonstrates the importance of semen cryobanking before beginning any cancer treatment. STUDY FUNDING/COMPETING INTERESTS: Supported by a grant from the Italian Ministry of Education and Research (MIUR-PRIN) and the University of Rome 'La Sapienza' Faculty of Medicine. The authors have no conflicts of interest.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedad de Hodgkin/patología , Infertilidad Masculina/inducido químicamente , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Infertilidad Masculina/complicaciones , Estudios Longitudinales , Masculino , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Estudios Retrospectivos , Análisis de Semen , Espermatozoides/patología , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversos
3.
Ann Oncol ; 25(7): 1404-1410, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24799461

RESUMEN

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Estudios de Cohortes , Femenino , Hepatitis C/complicaciones , Humanos , Linfoma de Células B/complicaciones , Masculino , Persona de Mediana Edad
4.
Ann Oncol ; 24(9): 2430-4, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23712545

RESUMEN

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.


Asunto(s)
Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/cirugía , Recurrencia Local de Neoplasia/mortalidad , Trasplante de Células Madre , Adolescente , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sobrevida , Trasplante Autólogo , Insuficiencia del Tratamiento , Adulto Joven
5.
Ann Oncol ; 23(2): 415-20, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21536660

RESUMEN

BACKGROUND: A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of (90)Y-ibritumomab tiuxetan ((90)Y-IT), 8-14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤ 25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received (90)Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. CONCLUSIONS: This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with (90)Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/radioterapia , Radioisótopos de Itrio/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Estudios Prospectivos , Radioinmunoterapia , Rituximab , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados
6.
Ann Oncol ; 22(7): 1628-1635, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21252060

RESUMEN

BACKGROUND: Epidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in pPCL. PATIENTS AND METHODS: A multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30). RESULTS: Sixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT. CONCLUSIONS: pPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Plasmáticas/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/administración & dosificación , Ácidos Borónicos/administración & dosificación , Bortezomib , Estudios de Cohortes , Terapia Combinada , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Pirazinas/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Talidomida/administración & dosificación , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
10.
Leukemia ; 20(10): 1840-7, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16932351

RESUMEN

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged

Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Irradiación Corporal Total
11.
Clin Ter ; 157(2): 105-9, 2006.
Artículo en Italiano | MEDLINE | ID: mdl-16817498

RESUMEN

AIMS: To analyze clinical and laboratory features at presentation in correlation to treatment response and overall survival; evaluation of different treatment approaches. METHODS: The data of 151 consecutive HCL patients observed between 1982 and 2005 were retrospectively analyzed. RESULTS: The following data at presentation were analyzed and compared to response, DFS, PFS and OS: Hb < 10 g/dl (observed in 27% of patients); Plt < 100,000/microl (72%); WBC > 10,000/microl (15%); Splenomegaly (75%); Bone marrow involvement > 70% (27%). At univariate analysis only WBC > 10,000/microl resulted significantly correlated to reduced PFS. 88 Pts received as first line treatment alpha2-interferon (IFN) alone, 49 purine analogues (PA) alone or in combination with IFN, 5 were treated with splenectomy. Among IFN treated patients CR, PR and SD were obtained in 21.6%, 73.8%, 4.5% respectively of the patients; while among PA treated patients in: 26.5%, 71.4%, 2.0% respectively. DFS was significantly prolonged in patients treated with PA with respect to IFN. No significant difference in OS was observed. Median PFS was 27.6 months, median OS is projected at 238 months after a median follow up of 131 months. CONCLUSIONS: Among the routine clinical and hematochemical baseline features only the presence of WBC > 10,000/microl was correlated to a lower PFS. First line treatment with purine analogues is correlated to prolonged PFS and DFS with respect to IFN; nevertheless no difference is observed in OS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Pilosas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Femenino , Estudios de Seguimiento , Hemoglobinas/metabolismo , Humanos , Interferón-alfa/administración & dosificación , Leucemia de Células Pilosas/sangre , Leucemia de Células Pilosas/mortalidad , Leucemia de Células Pilosas/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pentostatina/administración & dosificación , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Esplenectomía , Análisis de Supervivencia
12.
Leukemia ; 16(9): 1622-6, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12200673

RESUMEN

The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a follow-up of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Megacarioblástica Aguda/terapia , Adolescente , Adulto , Anciano , Niño , Terapia Combinada , Análisis Citogenético , Femenino , Humanos , Inmunofenotipificación , Leucemia Megacarioblástica Aguda/mortalidad , Leucemia Megacarioblástica Aguda/patología , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Resultado del Tratamiento
13.
Cancer Epidemiol Biomarkers Prev ; 5(3): 227-30, 1996 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8833624

RESUMEN

The relationship between acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia (CML), and refractory anemia with excess of blasts (RAEB) and antibodies to human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), and hepatitis B virus and hepatitis C virus (HCV) was investigated in a multicenter case-control study. There were 431 cases enrolled in the study at the time of diagnosis of hematological malignancies, and 862 controls ages 15 years or older were recruited in three hospitals. Antibodies to HTLV-I and HTLV-II, antibody to HCV, hepatitis B surface antigen, and antibody to hepatitis B core antigen were assayed. All cases and controls were negative for HTLV-1 antibodies; one case (1 of 431; 0.2%), and one control (1 of 862; 0.1%) were found positive for HTLV-II antibodies. A nonsignificant excess of risk for hepatitis B surface antigen was present among RAEB cases (odds ratio, 2.40; 95% confidence interval, 0.46--12) CML, (odds ratio, 2.70; 95% CI, 0.86--8.43), and between antibody of hepatitis B core antigen and AML (odds ratio, 1.40; 95% CI, 0.93-2.10). A weak, nonsignificant association was present between AML, acute lymphocytic leukemia, RAEB, and antibody to HCV. These preliminary results suggest a possible association (elevated odds ratios) between hepatitis B virus, AML, RAEB, and CML. However, because all confidence intervals overlapped the null value, these findings need to be confirmed in larger case-control studies.


Asunto(s)
Anticuerpos Anti-HTLV-I/análisis , Anticuerpos Anti-HTLV-II/análisis , Anticuerpos contra la Hepatitis B/análisis , Anticuerpos contra la Hepatitis C/análisis , Leucemia/virología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anemia Refractaria con Exceso de Blastos/virología , Estudios de Casos y Controles , Intervalos de Confianza , Femenino , Antígenos del Núcleo de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/virología , Leucemia Mieloide/virología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Factores de Riesgo
14.
Leuk Res ; 13(10): 883-91, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2685473

RESUMEN

Acute myeloblastic leukemia (AML) cells were cultured under conditions facilitating or preventing cell to cell contact. Proliferation of AML blasts of 24 patients was assessed in semisolid (containing 0.9% methylcellulose) and in liquid cultures, in which identical concentrations of colony stimulating factors (CSFs) had been provided. In all but one of the cases, significant DNA synthesis (evaluated by 3H-thymidine uptake) was observed when the cells were incubated in the liquid system, whereas in only 14 cases (58%), the cells were able to form clusters or colonies in the semisolid system. These findings suggest that AML cells from a large proportion of patients can proliferate only after stimulation with CSFs in a liquid system, i.e. when cultured under conditions permitting reciprocal contact between the cells. To establish further the importance of cell to cell contact for AML cell proliferation, cells from 19 patients were cultured in liquid medium concurrently in flat bottom microwells (in which a majority of the cells lie separate) and in round bottom microwells (in which cells show a tendency to aggregate). A significantly higher 3H-thymidine (TdR) incorporation in the round bottom cultures was observed in 15 out of 19 cases. The role of the leukocyte function antigens (LFA) LFA1, Mac1, P150-95 in this phenomenon was then analyzed, as these structurally related glycoproteins are involved in reactions requiring contact between hematopoietic cells. Membrane expression of the three antigens was first examined in 16 patients. LFA1, Mac1 and P150-95 were expressed on the AML cells of 15, 6 and 8 patients, respectively. Expression of these antigens did not change following short term incubation of the AML cells in the presence of CSFs. AML cells cultured in presence of saturating concentrations of monoclonal antibodies reacting with structures of these 3 antigens in order to abrogate their function did not suppress 3H-TdR uptake. Thus, no direct role for LFA1 and/or Mac1 and/or P150-95 antigens in mediating contact-induced AML proliferation could be demonstrated. It remains to be established which components are involved in the cell-cell contact-mediated upregulation of AML cell proliferation.


Asunto(s)
Antígenos CD/fisiología , Moléculas de Adhesión Celular/fisiología , Adhesión Celular , División Celular , Leucemia Mieloide Aguda/patología , Antígenos de Diferenciación/fisiología , ADN/biosíntesis , Humanos , Integrina alfaXbeta2 , Leucemia Mieloide Aguda/inmunología , Antígeno-1 Asociado a Función de Linfocito , Antígeno de Macrófago-1 , Receptores de Adhesión de Leucocito/fisiología
15.
Leuk Res ; 9(3): 407-12, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-3889507

RESUMEN

Thirteen patients with AML in first relapse were treated with high dose combination chemotherapy followed by cryopreserved autologous bone marrow transplantation (ABMT). The first four patients received the COATA-Roma regimen, consisting of CTX, VCR, CA, 6-TG and ADM; nine additional patients received the BAVC regimen consisting of BCNU, AMSA, VP-16 and CA. A median of 1.6 X 10(8) fractionated nucleated bone marrow cells/kg body weight were reinfused. The median of GM-CFU-C recovered was 4.7 X 10(4)/kg. Out of 13 patients, 10 (76.9%) achieved CR, 3 had profound aplasia and died from hemorrhagic or infectious complications. Of the 10 patients who achieved CR, 1 died after 1 week from heart failure, 5 relapsed respectively 17, 20, 21, 21, 42, weeks after ABMT, 4 are still in CR after 2+, 14+, 17+, and 120+, weeks. Of the 9 patients treated with BAVC regimen, 8(88.8%) achieved CR. Four patients relapsed after a median of 19.7 weeks and 4 are still in complete remission. Of interest is the fact that the second complete remission of one patient is longer than the first one, despite the fact that marrow was not purified by any in vitro treatment. In conclusion we can say that BAVC regimen is highly effective in obtaining second complete remission in patients with AML and prolonged disease free survival can be achieved at least in a small number of cases.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Conservación de Tejido , Adolescente , Adulto , Niño , Terapia Combinada , Femenino , Congelación , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Factores de Tiempo
16.
Leuk Res ; 8(4): 729-35, 1984.
Artículo en Inglés | MEDLINE | ID: mdl-6471902

RESUMEN

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.


Asunto(s)
Asparaginasa/administración & dosificación , Citarabina/administración & dosificación , Leucemia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Adolescente , Adulto , Quimioterapia Combinada , Humanos
17.
Leuk Res ; 11(3): 265-72, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-3550300

RESUMEN

Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfusion of S4-7 purged cells, regeneration of marrow cells occurred with prompt recovery of granulopoiesis and erythropoiesis. A more delayed platelet recovery was observed. The two patients are in complete remission at 20 and 11 months from ABMT. The results indicate that immunologic purging with S4-7 MoAb is safe and suitable for selected AML patients undergoing ABMT.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Trasplante de Médula Ósea , Proteínas del Sistema Complemento/inmunología , Leucemia Mieloide Aguda/terapia , Antígeno Lewis X/inmunología , Oligosacáridos/inmunología , Adolescente , Adulto , Animales , Antígenos de Superficie/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Femenino , Hematopoyesis , Humanos , Leucemia Mieloide Aguda/inmunología , Masculino , Conejos , Trasplante Autólogo
18.
Semin Arthritis Rheum ; 26(6): 845-9, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9213384

RESUMEN

OBJECTIVE: The association of systemic lupus erythematosus (SLE) and multiple myeloma (MM) is an uncommon event. We report the relapse of SLE in a patient with a previous history of MM, treated with chemotherapy and, subsequently, with alpha-2b interferon (alpha-2b IFN) as a maintenance therapy. The case is discussed in light of past relevant literature. METHODS: The history and clinical, laboratory and radiographic findings of the patient, as well as the subsequent therapeutic approach are discussed. In our review of the literature, journal articles are identified by Medline search. RESULTS: We describe the case of a woman who developed a multiple myeloma 14 years after a diagnosis of SLE. A careful literature review confirms that the association of these two diseases has been reported only in a few cases. When the plasma cell neoplasia occurred, SLE had been quiescent for several years; the patient was treated with prednisone-melphalan and, subsequently, with alpha-2b IFN as a maintenance therapy. On admission to our department, SLE was in a relapse phase, probably because of IFN treatment. The disease was poorly responsive to steroid therapy and required the use of cytotoxic drugs. CONCLUSIONS: The coexistence of SLE and MM is very rare and the possible pathogenetic mechanisms underlying this association remain unclear. The use of interferon in a patient with an autoimmune disease always invites caution.


Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Mieloma Múltiple/complicaciones , Antineoplásicos/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/patología , Melfalán/uso terapéutico , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Proteínas Recombinantes , Recurrencia
19.
Bone Marrow Transplant ; 2(3): 287-98, 1987 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3502785

RESUMEN

The efficacy of autologous bone marrow transplantation in leukemia and lymphoma may depend upon the selective elimination of malignant cells from human bone marrow in vivo and in vitro. A cyclophosphamide derivative (ASTA-Z 7654) and etoposide (VP16-213) have been tested on lymphoma and leukemia cell lines in a model that may represent a bone marrow situation in complete remission. The influence of different concentrations of normal mononuclear cells and tumor cells in this model and the activity of the two chemotherapeutic agents in the presence of bone marrow cells or peripheral blood cells were evaluated. A major inhibitory effect was observed using the two agents in combination; low doses of ASTA-Z and VP16 consecutively added to the mixture of malignant cells and normal mononuclear cells resulted in a greater elimination of tumor line cells than with ASTA-Z alone at the current 100 micrograms/ml dose. In contrast, no major toxicity on normal human bone marrow precursors was observed; the effect of treatment on hemopoietic recovery with the two agents either alone or in combination was evaluated on CFU-GM growth after long-term bone marrow cultures. Despite a profound growth inhibition at day 0, a recovery was observed in all cases after 7 or 14 days. The use of multiple chemotherapeutic agents in the treatment of bone marrow in vitro could decrease the possibility of malignant cells surviving while sparing normal bone marrow precursors.


Asunto(s)
Médula Ósea/efectos de los fármacos , Ciclofosfamida/análogos & derivados , Etopósido/administración & dosificación , Células de la Médula Ósea , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Técnicas In Vitro , Células Tumorales Cultivadas
20.
Bone Marrow Transplant ; 4(6): 669-74, 1989 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-2819285

RESUMEN

A mouse monoclonal antibody (S4-7) reacting with human myelomonocytic cells has been previously shown to be suitable for bone marrow purging in selected acute myelogenous leukemia (AML) patients with S4-7 positive leukemic clonogenic cells at diagnosis. The results obtained in seven AML patients who underwent such a treatment, followed by autologous bone marrow transplantation (ABMT), are now reported. Six patients underwent ABMT in first complete remission (CR), one in second CR, after BAVC conditioning regimen. One patient died of infection 1 month after ABMT; in the other six a complete recovery of hemopoiesis was observed. In spite of S4-7 reactivity with normal myelomonocytic cells, a prompt recovery of granulopoiesis was however observed both in in vitro liquid culture and in vivo with a median time of 20 days to reach granulocyte values of 500 x 10(6)/l. The patient transplanted in 2nd CR relapsed 3 months after ABMT. Of the five evaluable patients transplanted in 1st CR, two relapsed 8 and 9 months post-ABMT while three remain in continuous CR at 35, 47, 57 months. Leukemic cells of two of the three patients with recurrent disease were studied at relapse and in both could be detected a significant percentage of S4-7 negative cells, detectable neither at diagnosis nor (one patient) at the time of first relapse after standard chemotherapy.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos de Diferenciación Mielomonocítica/inmunología , Trasplante de Médula Ósea/métodos , Leucemia Mieloide Aguda/cirugía , Antígenos de Neoplasias/inmunología , Ensayo de Unidades Formadoras de Colonias , Fucosa/inmunología , Hematopoyesis , Humanos , Lactosa/inmunología , Leucemia Mieloide Aguda/inmunología
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