RESUMO
The diagnosis of Waldenström macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM.
Assuntos
Macroglobulinemia de Waldenstrom/diagnóstico , Comitês Consultivos , Humanos , Londres , Guias de Prática Clínica como AssuntoRESUMO
This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials.
Assuntos
Macroglobulinemia de Waldenstrom/tratamento farmacológico , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Antimetabólitos/uso terapêutico , Exame de Medula Óssea/métodos , Exame de Medula Óssea/normas , Ácidos Borônicos/uso terapêutico , Bortezomib , Densitometria , Progressão da Doença , Intervalo Livre de Doença , Previsões , Hematopoese , Humanos , Cadeias Leves de Imunoglobulina/sangue , Imunoglobulina M/sangue , Imunossupressores/uso terapêutico , Neoplasia Residual , Nefelometria e Turbidimetria , Tomografia por Emissão de Pósitrons , Pirazinas/uso terapêutico , Indução de Remissão , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/patologiaRESUMO
In this issue of Blood, Berentsen and coworkers describe a high response rate which is durable in some patients who receive combination fludarabine and rituximab for chronic cold agglutinin disease (CAD). If confirmed, this is a significant advance in therapy for a frequently difficult clinical problem.
RESUMO
PURPOSE: CD40 ligand (CD40L, CD154) plays a central role in immunoregulation and also directly modulates epithelial cell growth and differentiation. We previously showed that the CD40 receptor is commonly expressed in primary breast cancer tissues. In this proof-of-principle study, we examined the breast cancer growth-regulatory activities of an oncolytic adenoviral construct carrying the CD40L transgene (AdEHCD40L). EXPERIMENTAL DESIGN: In vitro and in vivo evaluations were carried out on AdEHCD40L to validate selective viral replication and CD40L transgene activity in hypoxia inducing factor-1alpha and estrogen receptor-expressing human breast cancer cells. RESULTS: AdEHCD40L inhibited the in vitro growth of CD40+ human breast cancer lines (T-47D, MDA-MB-231, and BT-20) by up to 80% at a low multiplicity of infection of 1. Incorporation of the CD40L transgene reduced the effective dose needed to achieve 50% growth inhibition (ED50) by approximately 10-fold. In contrast, viral and transgene expression of AdEHCD40L, as well its cytotoxicity, was markedly attenuated in nonmalignant cells. Intratumoral injections with AdEHCD40L reduced preexisting MDA-MB-231 xenograft growth in severe combined immunodeficient mice by >99% and was significantly more effective (P<0.003) than parental virus AdEH (69%) or the recombinant CD40L protein (49%). This enhanced antitumor activity correlated with cell cycle blockade and increased apoptosis in AdEHCD40L-infected tumor cells. CONCLUSIONS: These novel findings, together with the previously known immune-activating features of CD40L, support the potential applicability of AdEHCD40L for experimental treatment of human breast cancer.
Assuntos
Adenoviridae/genética , Neoplasias da Mama/terapia , Ligante de CD40/genética , Terapia Genética/métodos , Transgenes , Proteínas E1A de Adenovirus/análise , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos SCID , Fenótipo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
William Osler died on December 29, 1919, at the age of 70. Less than 1 year later, Frederick Grant Banting began a research project at the University of Toronto to find a treatment for diabetes mellitus. John James Rickard Macleod, director of physiology, gave him space, funding, and supplies. Charles Herbert Best, an undergraduate medical student, joined Banting. In 1921, Banting and Best isolated and purified insulin from pancreatic extracts of dogs. James Bertram Collip, a biochemist, helped in the purification process. The first American patient was treated with Toronto insulin in May 1922. Banting and Macleod were awarded the Nobel Prize in 1923 "for the discovery of insulin." George Richards Minot, a young hematologist in Boston, had an obsessive interest in the effect of diet on anemia. In October 1921, Minot developed weight loss and was diagnosed with severe diabetes mellitus. By January 1923, the pioneering diabetologist, Elliott Proctor Joslin, began to treat Minot with insulin. Minot's condition improved and he returned to work. In 1926, Minot and William Parry Murphy amazed the medical world when they eradicated anemia in 45 pernicious anemia patients by feeding them a half-pound of beef liver daily. Minot shared the 1934 Nobel Prize with Murphy and George Hoyt Whipple "for their discoveries concerning liver therapy in cases of anemia." Minot remained on insulin the rest of his life. Osler described the clinical findings and blood picture of pernicious anemia nearly a half century before Minot but his observations were largely ignored. Osler had an intriguing connection to Banting. Had he lived, Osler would have been ecstatic over these two monumental therapeutic breakthroughs.
RESUMO
We present the case of a 50-year-old Hispanic man who presented to the emergency department with an acute right femur fracture after 3 months of intermittent discomfort in the right leg. He was eventually diagnosed with immunoglobulin D (IgD) multiple myeloma, a rare class of myeloma that is often of advanced stage at diagnosis. Fortunately, our patient was stage I at diagnosis and did not have hypercalcemia, anemia, or renal insufficiency, as is common with myeloma. This report describes a rare case of an uncommon condition and highlights the fortunate aspects of this patient's unfortunate diagnosis.
Assuntos
Viscosidade Sanguínea , Plasmaferese , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/terapia , Idoso , Crioglobulinemia/sangue , Crioglobulinas/metabolismo , Medicina Baseada em Evidências , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/terapia , Humanos , Masculino , Oftalmoscópios , Doenças Retinianas/sangue , Doenças Retinianas/diagnóstico , Doenças Retinianas/terapia , SíndromeRESUMO
Hyperviscosity syndrome (HVS) is a common manifestation of Waldenström's macroglobulinemia (WM). Patients with HVS have skin and mucosal bleeding, retinopathy with visual disturbances, and a variety of neurologic disorders. HVS can be diagnosed from physical examination by identifying the characteristic retinal venous engorgement ("sausaging") on funduscopic inspection. HVS can be accurately monitored with an Ostwald tube and reversed by plasmapheresis. Cryoglobulins precipitate or gel at temperatures < 37 degrees C and dissolve on re-warming. They may be composed of single or multiple components. Most cryoglobulins are mixed monoclonal IgMpolyclonal IgG immune complexes and many are associated with hepatitis C viral infection. Monoclonal macroglobulin autoreactive antibodies are included among the "IgM-related" disorders that influence the clinical presentation and natural history of WM.
Assuntos
Viscosidade Sanguínea , Crioglobulinemia/sangue , Crioglobulinas/metabolismo , Macroglobulinemia de Waldenstrom/sangue , Crioglobulinemia/imunologia , Crioglobulinemia/patologia , Humanos , Vasos Retinianos/patologia , Macroglobulinemia de Waldenstrom/imunologia , Macroglobulinemia de Waldenstrom/patologiaRESUMO
William Osler's address, The Reserves of Life, was given to students at St Mary's Hospital Medical School in London in 1907. In the talk Osler likened a medical career to a race through London, pointing out that to be successful one had to have sufficient 'reserves' or staying powers. He also commented on several of his favourite topics and included some of his most memorable aphorisms. Almroth Wright was the colourful and controversial physician at St Mary's Hospital who described opsonins and was a strong advocate of vaccine therapy for bacterial infections. Wright was often critical of clinicians and scoffed at their crude methods. During the address to the St Mary's students, Osler abruptly departed from his theme to criticize Wright ('that Celtic Siren') and defend clinicians, emphasizing that the art and science of medicine were inseparable. Despite their differences, Osler and Wright maintained a cordial relationship.
Assuntos
Aforismos e Provérbios como Assunto , Pesquisa Biomédica/história , Docentes de Medicina/história , Editoração/história , Docentes de Medicina/normas , História do Século XIX , História do Século XX , Humanos , LondresRESUMO
This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/métodos , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína de Bence Jones/análise , Transplante de Medula Óssea/efeitos adversos , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imunoglobulina M/análise , Cooperação Internacional , Masculino , Prognóstico , Medição de Risco , Prevenção Secundária , Índice de Gravidade de Doença , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento , Estados Unidos , Macroglobulinemia de Waldenstrom/terapiaRESUMO
John Finney (1863-1942) was born near Natchez, Mississippi. After receiving his medical degree from Harvard, he interned at Massachusetts General Hospital and then went to Baltimore to become one of the first interns at the new Johns Hopkins Hospital. He met William Osler the day the hospital opened and became a lifelong admirer of "the Chief." Finney specialized in gastrointestinal surgery and was recognized for his expertise in the field. Osler recommended Finney to a physician colleague, writing, "You could not be in better hands . Finney has been most successful and his judgment is so good." Finney served for 33 years under William Halsted at Hopkins. After Halsted's death, Finney was offered the chair of surgery at Johns Hopkins but declined. He was a founder and first president of the American College of Surgeons. He also served as president of the American Surgical Association and the Society of Clinical Surgery. Finney became chief surgical consultant for the Allied Expeditionary Forces in World War I. He was decorated by the United States, France, and Belgium. Finney was a master surgeon and a role model for generations of students and physicians.
RESUMO
Some monoclonal proteins from patients with Waldenstrom's macroglobulinemia (WM) or immunoglobulin (Ig) M monoclonal gammopathy of undetermined significance possess antigen-binding activity directed to autogenous or foreign antigens. These monoclonal IgM autoantibodies include cold agglutinins, mixed cryoglobulins, and antineural components. Because of the antigenantibody interaction, patients with these autoimmune syndromes often present with hemolytic anemia, mixed cryoglobulinemia, or peripheral neuropathy, respectively, at an earlier stage than patients with typical WM who do not have evident antibody activity. The presence of monoclonal macroglobulin autoreactive antibodies thus influences clinical presentation and natural history. Monoclonal IgM antibodies display polyreactivity to antigens of microbial origin in addition to autogenous antigens and may arise through T-independent as well as T-dependent pathways. Waldenstrom proteins with antibody activity appear to provide a link between autoimmunity, infection, and lymphoproliferative disease. Study of the antigens reacting with monoclonal IgMs may provide further insight into the pathogenesis of WM.
Assuntos
Autoanticorpos/imunologia , Imunoglobulina M/imunologia , Macroglobulinemia de Waldenstrom/imunologia , Aglutininas/imunologia , Linfócitos B/imunologia , Crioglobulinas/imunologia , Humanos , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/patologia , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Immunoglobulin (Ig) M myeloma is a distinct entity with features of multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). The malignant cells in IgM myeloma have a distinctive chromosomal translocation that differentiates them from WM. These cells are postgerminal-center in origin with isotype-switch transcripts. They appear to be arrested at a point of maturation between that of WM and MM. Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma. Additional studies on patients with this rare tumor may provide further insight into the pathogenesis of bone disease in plasma cell dyscrasias.
Assuntos
Imunoglobulina M/genética , Imunoglobulina M/imunologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/imunologia , Diferenciação Celular , Citocinas/biossíntese , Glicoproteínas/biossíntese , Humanos , Linfocinas/biossíntese , Masculino , Pessoa de Meia-Idade , Osteoprotegerina , Receptores Citoplasmáticos e Nucleares/biossíntese , Receptores do Fator de Necrose Tumoral , Translocação GenéticaRESUMO
CD40, a member of the tumor necrosis factor receptor (TNF-R) family, is a surface receptor best known for its capacity to initiate multifaceted activation signals in normal B cells and dendritic cells (DCs). CD40-related treatment approaches have been considered for the experimental therapy of human leukemias, lymphomas, and multiple myeloma, based on findings that CD40 binding by its natural ligand (CD40L), CD154, led to growth modulation of malignant B cells. Recent studies also exploited the selective expression of the CD40 receptor on human epithelial and mesenchymal tumors but not on most normal, nonproliferating epithelial tissues. Ligation of CD40 on human breast, ovarian, cervical, bladder, non small cell lung, and squamous epithelial carcinoma cells was found to produce a direct growth-inhibitory effect through cell cycle blockage and/or apoptotic induction with no overt side effects on their normal counterparts. CD154 treatment also heightened tumor rejection immune responses through DC activation, and by increasing tumor immunogenicity through up-regulation of costimulatory molecule expression and cytokine production of epithelial cancer cells. These immunopotentiating features can produce a "bystander effect" through which the CD40-negative tumor subset is eliminated by activated tumor-reactive cytotoxic T cells. However, the potential risk of systemic inflammation and autoimmune consequences remains a concern for systemic CD154-based experimental therapy. The promise of CD154 as a tumor therapeutic agent to directly modulate tumor cell growth, and indirectly activate antitumor immune response, may depend on selective and/or restricted CD154 expression within the tumor microenvironment. This may be achieved by inoculating cancer vaccines of autologous cancer cells that have been transduced ex vivo with CD154, as documented by recently clinical trials. This review summarizes recent findings on CD154 recombinant protein- and gene therapy-based tumor treatment approaches, and examines our understanding of the multifaceted molecular mechanisms of CD154-CD40 interactions.
Assuntos
Antígenos CD40/fisiologia , Ligante de CD40/fisiologia , Terapia Genética , Imunoterapia , Neoplasias/terapia , Animais , Apoptose , Ligante de CD40/metabolismo , Ensaios Clínicos como Assunto , Células Dendríticas/imunologia , Humanos , CamundongosRESUMO
Assays for specific antigen-binding activity were performed on sera from 172 patients with monoclonal macroglobulinemia defined by immunofixation electrophoresis. The sera were collected between 1970 and 2002. Mean IgM level was 1,409 mg/dL with a range from 70 to 6,800. Cryoglobulins were identified in 15.3% (26/170 sera: 12 trace, five single component, and nine mixed IgM-IgG). Rheumatoid factor (RF) was detected in 19 of 151 (12.6%) samples with titers ranging from 1:80 to 1:327,680. Among the nine mixed IgM-IgG cryos, eight were RF-positive and six of six displayed positivity for hepatitis C virus. Cold agglutinins (CA) were present in 8.5% (10/117) of sera with anti-I titers between 1:512 and 1:65,536. IgM binding to a series of glycosaminoglycan oligosaccharides, glycolipids, and glycoprotein antigens was found in 75 samples (43%). IgM binding to antigens having known associations to polyneuropathies occurred in 20 patients (12%). Antinuclear antibody (ANA) was documented in 10.7% (18/169) of sera. Anti-DNA activity was absent in all samples tested. Sera from 71% of patients with monoclonal macroglobulinemia in this series exhibited binding to autoantigens. Some of these immune complexes resulted in clinically significant manifestations. Our results suggest that many monoclonal immunoglobulins may be functional antibodies rather than "paraproteins." Characterization of antigen-binding activities may provide insight into the pathogenesis of monoclonal gammopathies.
Assuntos
Anticorpos/sangue , Macroglobulinemia de Waldenstrom/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aglutininas/sangue , Anticorpos Antinucleares/sangue , Crioglobulinas , Feminino , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangue , Macroglobulinemia de Waldenstrom/sangueRESUMO
This presentation represents consensus recommendations on prognostic markers and criteria to initiate therapy in patients with Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the Second International Workshop held in Athens, Greece during September 2002. The panel recommended that initiation of therapy should not be based on the IgM level per se since this may not correlate with the clinical manifestations of WM. The consensus panel agreed that initiation of therapy was appropriate for patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, or weight loss. The presence of progressive, symptomatic lymphadenopathy or splenomegaly provide additional reasons to begin therapy. The presence of anemia with a hemoglobin value of Assuntos
Macroglobulinemia de Waldenstrom/diagnóstico
, Macroglobulinemia de Waldenstrom/terapia
, Fatores Etários
, Anemia
, Biomarcadores/sangue
, Hemoglobinas/metabolismo
, Humanos
, Imunoglobulina M/metabolismo
, Doenças Linfáticas
, Guias de Prática Clínica como Assunto
, Prognóstico
, Esplenomegalia
, Macroglobulinemia de Waldenstrom/mortalidade
, Redução de Peso
, Microglobulina beta-2/metabolismo
RESUMO
BACKGROUND: Patients who undergo orthotopic liver transplantation (OLT) for Budd-Chiari syndrome (BCS) traditionally have been anticoagulated with warfarin postoperatively. Because a significant proportion of BCS patients are found to have an underlying myeloproliferative disorder (MPD), antiplatelet therapy may be a more rational treatment strategy for this subgroup. METHODS: All patients who underwent OLT for the diagnosis of BCS at our institution through March 2000 were included in this analysis. Posttransplant therapy consisted of hydroxyurea and aspirin for those with MPDs. Standard anticoagulation or no antithrombotic treatment was given to BCS patients with other causes. Major posttransplantation complications (thrombosis and bleeding) and mortality were determined. RESULTS: Seventeen patients underwent OLT for BCS at our institution. The mean follow-up was 68.4 months. Two of seventeen patients died; one patient died of recurrent thrombosis (124 months after OLT) and the other patient died of acute hepatitis B (7 months after OLT). Twelve patients (71%) had evidence of a MPD. Two of the MPD patients were treated with warfarin before the initiation of hydroxyurea and aspirin therapy. The remaining 10 MPD patients were placed on only hydroxyurea and aspirin after OLT. Anagrelide was used in place of hydroxyurea in two patients because of cytopenias caused by the latter agent. The mean follow-up of this group of 10 patients was 59.9 months. Only one patient experienced recurrent thrombosis, which occurred more than 10 years after the original transplant. There were no major bleeding complications and posttransplant liver biopsies were well tolerated. CONCLUSIONS: Antiplatelet therapy that consists of hydroxyurea and aspirin is a safe and effective alternative to anticoagulation to prevent recurrent thrombosis in MPD patients with BCS after liver transplantation. For patients with a hypercoagulable state corrected by OLT, antithrombotic therapy probably is not required. For those patients with conditions not corrected by OLT or with idiopathic BCS, anticoagulation or other therapy to control the hypercoagulable state should be given.
Assuntos
Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/cirurgia , Transplante de Fígado , Policitemia Vera/complicações , Policitemia Vera/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Síndrome de Budd-Chiari/sangue , Inibidores Enzimáticos/administração & dosagem , Fator V , Feminino , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores da Agregação Plaquetária/administração & dosagem , Protrombina/genética , Sarcoidose/complicaçõesRESUMO
BACKGROUND: Graft-versus-host disease (GVHD) is an important, underdiagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD among 1,082 liver transplantations performed in patients at our institution between 1991 and 1998. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Treatment generally involved increased immune suppression and hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte monocyte colony stimulating factor); however, all but one patient died, most often from sepsis. Early in its course, GVHD was difficult to distinguish from cytomegalovirus disease or drug reactions. The diagnosis was confirmed by demonstration of substantial donor lymphoid chimerism. METHODS: To identify risk factors for severe GVHD, a retrospective analysis was performed comparing index cases with the rest of the cases in our institutional experience. RESULTS: Closely matched human leukocyte antigen recipients, those older than 65 years, and recipients with donors more than 40 years younger were at higher risk for GVHD. One case occurred in a patient with a congenital immunodeficiency. CONCLUSIONS: Liver transplant-associated GVHD is a progressive and fatal disease. Future approaches should focus on prevention and might include avoidance of closely matched human leukocyte antigen donors, treatment of the donor to reduce the number of lymphocytes, or reduction of immunosuppression in the early posttransplant period.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/terapia , Teste de Histocompatibilidade , Humanos , Síndromes de Imunodeficiência/congênito , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
This prospective clinical trial was designed to assess the impact of adjuvant chemotherapy in women with rapidly proliferating node-negative breast cancer. This group has been predicted to have a 5-year disease-free survival (DFS) of 70% without adjuvant chemotherapy. In this study, 449 women with rapidly proliferating breast cancer (91% measured by S-phase fraction and 9% by histochemistry) received adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) plus tamoxifen for estrogen receptor-positive or progesterone receptor-positive cancer. The 5-year DFS was 90% (+/- 2%) and the 5-year overall survival was 94% (+/- 1%). At a median follow-up of 62 months, the strategy of administering 6 cycles of AC to women with T2 N0 cancer and 3 cycles in those with smaller T1 N0 cancers appeared to eliminate tumor size as a potential prognostic factor. Adjuvant chemotherapy with AC appears effective in reducing recurrence rates for women with rapidly proliferating node-negative breast cancer.