ABSTRACT
Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
Subject(s)
Antineoplastic Agents/therapeutic use , Hematopoietic Stem Cell Transplantation , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Protein Kinase Inhibitors/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Family , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Prognosis , Prospective Studies , Remission Induction , Risk , Survival Analysis , Tissue Donors , Transplantation, Homologous , Treatment OutcomeSubject(s)
Antineoplastic Agents/administration & dosage , Imidazoles/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Pyridazines/administration & dosage , Stem Cell Transplantation , Adult , Allografts , Female , Humans , Middle Aged , RecurrenceABSTRACT
BACKGROUND: Targeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer. PATIENTS AND METHODS: Patients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m(2) q3w). Primary end points were safety and tolerability. Antitumor activity was evaluated according to RECIST. Clinical benefit was defined as complete or partial response or stable disease for ≥24 weeks. RESULTS: Thirty-one evaluable patients were treated. Most adverse events were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated doses of adecatumumab given in combination with docetaxel were 550 mg/m(2) q3w and 360 mg/m(2) qw. Clinical benefit was observed in 44% of patients treated with q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM-expressing tumors. CONCLUSION: Combination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.
Subject(s)
Antigens, Neoplasm/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cell Adhesion Molecules/metabolism , Drug Resistance, Neoplasm , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Adhesion Molecules/administration & dosage , Docetaxel , Drug Administration Schedule , Epithelial Cell Adhesion Molecule , Female , Humans , Leukocyte Disorders/chemically induced , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
The understanding of hereditary vascular anomalies was hampered for a long time by unclear und unspecific terminology. Today, the classification of the International Society for the Study of Vascular Anomalies (ISSVA) differentiates between vascular tumours (mostly infantile haemangioma) with active endothelial proliferation and regression and vascular malformations (VM), which are defects of the vascular morphogenesis and are distinguished in predominantly venous, arterial, capillary, lymphatic, arteriovenous or combined VM. Symptoms are pain, swelling and restricted movement, accompanied by skin signs like dys-plastic veins and capillary VM (naevus flammeus). Thrombophlebitis and chronic venous insufficiency are related to venous VM. Arteriovenous VM are progressive and can cause ischaemic necroses, in rare cases even a high-output cardiac fail-ure. Lymphatic VM lead to localised swelling, in the long run often to recurrent erysipelas and lymphorroea. Primary imaging is provided by -ul-trasound including flow measurements. Mor-phol-ogy and organ involvement is best delineated by magnetic resonance imaging. Phlebography is used to image deep venous system anomalies and is always accompanied by varicography of the dysplastic parts of the venous VM. Digital subtraction angiography is performed to demon-strate the flow pattern in feeding arteries, the nidus and the drainage veins of arteriovenous VM. Besides size and localisation the prognosis of the patients is determined by the pressure (the high-er the pressure, the poorer the prognosis) and the flow rate (the higher the flow rate, the poorer the prognosis) in the VM. Diagnosis and treatment of these rare diseases are best performed in special-ised, interdisciplinary centres.
Subject(s)
Vascular Malformations/classification , Vascular Malformations/genetics , Angiography, Digital Subtraction , Arteriovenous Malformations/classification , Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/genetics , Hemangioma/classification , Hemangioma/diagnosis , Hemangioma/genetics , Humans , Lymphatic Abnormalities/classification , Lymphatic Abnormalities/diagnosis , Lymphatic Abnormalities/genetics , Magnetic Resonance Angiography , Port-Wine Stain/classification , Port-Wine Stain/diagnosis , Port-Wine Stain/genetics , Prognosis , Skin Neoplasms/classification , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Societies, Medical , Soft Tissue Neoplasms/classification , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/genetics , Ultrasonography , Vascular Malformations/diagnosis , Veins/abnormalitiesABSTRACT
In AML, a complex aberrant karyotype is associated with poor response to chemotherapy and dismal prognosis. We prospectively studied the concept of allogeneic haematopoietic SCT (HSCT), performed early and regardless of response to induction treatment in patients with complex karyotype AML (CK-AML). The preparative regimen consisted of fludarabine, Ara-C and amsacrine (FLAMSA) chemotherapy, followed by reduced intensity conditioning (RIC) 3 days later. In vivo T-cell depletion by anti-thymocyte globulin was used to protect from early GvHD, and prophylactic donor lymphocyte transfusion was given from day+120 to augment the GvL effect, once tolerance was established. Eighteen consecutive patients with CK-AML (median age: 53 years) received HSCT from related (n=7) or unrelated (n=11) donors. Before FLAMSA-RIC, nine patients each had received one and two induction courses. Stage at start of FLAMSA-RIC was CR/CRi (n=8) or persistent disease (n=10). Following HSCT, 16 patients achieved CR. After a follow-up of 51 months, 11 patients are alive in CR, whereas seven have died in remission (n=3), or from leukaemia (n=4). Cumulative incidence of relapse, non-relapse mortality, acute GvHD≥II and chronic GvHD were 0.222±0.098, 0.235±0.104, 0.367±0.120 and 0.481±0.123, respectively. Four-year survival from HSCT is 61%. Early HSCT following FLAMSA-RIC may improve the outcome of this unfavourable AML subgroup.
Subject(s)
Abnormal Karyotype , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Transplantation Conditioning/methods , Acute Disease , Adolescent , Adult , Amsacrine/administration & dosage , Amsacrine/adverse effects , Antilymphocyte Serum , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Cytarabine/administration & dosage , Cytarabine/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/genetics , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Graft vs Host Disease/therapy , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Lymphocyte Depletion/adverse effects , Lymphocyte Depletion/methods , Male , Middle Aged , Pilot Projects , Prospective Studies , Survival Rate , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Vidarabine/administration & dosage , Vidarabine/adverse effects , Vidarabine/analogs & derivativesABSTRACT
BACKGROUND: To study the effects of deferring pegfilgrastim until day 4 on the reduction of chemotherapy-induced leukocytopenia. PATIENTS AND METHODS: Patients of age 61-80 years with aggressive lymphoma were randomly assigned to receive 6 mg pegfilgrastim on day 2 or 4 of a 2-week chemotherapy regimen (R-CHOP-14). RESULTS: Two hundred and ninety-two and 313 chemotherapy cycles were evaluable in 103 patients. Post-nadir pegfilgrastim serum levels were higher after day 4 than after day 2 application. This was associated with an attenuated leukocyte nadir after day 4 pegfilgrastim and there were fewer days with leukocytes <2 × 10(3)/mm(3) compared with day 2 pegfilgrastim. Grade 3 and 4 leukocytopenias (70% versus 43.3%; P < 0.001) and grade 4-only leukocytopenias (47% versus 20.5%; P < 0.001) were more frequent after day 2 pegfilgrastim. There were more chemotherapy cycles with grade 3 and 4 infections after day 2 than day 4 pegfilgrastim (9.4% versus 6.0%; P = 0.118). Interventional antibiotics were given more often after day 2 than after day 4 pegfilgrastim (30.7% versus 21.9% of cycles; P = 0.008). There were five deaths during leukocytopenia after day 2 and none after day 4 pegfilgrastim (P = 0.027). CONCLUSIONS: Administration of pegfilgrastim on day 4 was more effective in reducing severe leukocytopenias and resulted in fewer deaths during leukocytopenia. Pegfilgrastim should be given on day 4 to better exploit its myeloprotective potential.
Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Leukopenia/prevention & control , Lymphoma/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Drug-Related Side Effects and Adverse Reactions , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/adverse effects , Granulocyte Colony-Stimulating Factor/blood , Humans , Leukocyte Count , Leukopenia/chemically induced , Leukopenia/mortality , Male , Middle Aged , Neoplasm Staging , Polyethylene Glycols , Prednisone/administration & dosage , Prednisone/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/blood , Vincristine/administration & dosage , Vincristine/therapeutic useABSTRACT
Painful pink or magenta colored skin lesions characterized by a clear line of demarcation between the affected area and surrounding tissue appearing under therapy with coumarins may be a sign for evolving coumarin-necrosis. Immediate treatment with a protein C preparation in patients with protein C deficiency can prevent necrosis.
Subject(s)
Coumarins/adverse effects , Protein C Deficiency/chemically induced , Protein C Deficiency/drug therapy , Protein C/administration & dosage , Adult , Anticoagulants/adverse effects , Female , Humans , Necrosis/chemically induced , Necrosis/drug therapyABSTRACT
Tumor diseases can be accompanied by paraneoplastic syndromes. Low platelet counts and hyperfibrinolysis led to the diagnosis of recurrent breast cancer in this case. A tumour disease with disturbed hemostasis caused by both plasmatic coagulation and thrombocytopenia has not yet been reported.
Subject(s)
Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Fibrinolysis , Hemorrhagic Disorders/complications , Hemorrhagic Disorders/diagnosis , Thrombocytopenia/complications , Thrombocytopenia/diagnosis , Aged , Female , Humans , Paraneoplastic Syndromes/complications , Paraneoplastic Syndromes/diagnosisABSTRACT
PURPOSE: We examined how often ultrasound-guided core needle biopsies of lymph nodes yield subclassification of malignant lymphoma according to World Health Organization (WHO) criteria and help to avoid excisional biopsies. MATERIALS AND METHODS: The prospective study included 124 consecutive patients in whom 126 core needle biopsies of lymph nodes were performed to diagnose or rule out malignant lymphoma. If possible, we obtained 5 cylinders with a 14-gauge (G) needle. The pathologists of our institution, partly in cooperation with a lymphoma registry, decided whether a core needle biopsy was sufficient for subclassification or an excisional biopsy was necessary. RESULTS: 95 of the 126 core needle biopsies (76.6 %) were performed with a 14-G needle. In 101 biopsies (80.2 %), we obtained at least 5 cylinders. In 120 of the 126 core needle biopsies (95 %), malignant lymphoma was diagnosed and subclassified or ruled out. Of the 64 lymphoma, 60 (94 %) were subclassified. Among them were 41 (93 %) of the 44 primary lymphomas and 19 (95 %) of the 20 recurrent lymphomas. In 5 of 126 cases (4 %), an excisional biopsy was necessary. CONCLUSION: With ultrasound-guided core needle biopsy of lymph nodes, lymphoma can be reliably diagnosed and subclassified if preferably 5 cores are obtained with 14-G needles. Excisional biopsy is rarely necessary if core needle biopsy is inconclusive.
Subject(s)
Biopsy, Needle/methods , Lymph Nodes/pathology , Lymphoma/pathology , Humans , Lymph Nodes/diagnostic imaging , Lymphoma, B-Cell/pathology , Prospective Studies , UltrasonographyABSTRACT
BACKGROUND: This investigation intended to study the unspecific background to be expected in normal bone marrow (BM), comparing three well recognized protocols for immunocytochemical detection of disseminated carcinoma cells. The interlaboratory variation in screening and evaluation of stained cells was analyzed and different screening methods were compared. METHODS: BM mononuclear cells (BM MNC) from 48 normal BMs were immunostained in parallel by three participating laboratories. The protocols, based on three different anti-cytokeratin antibodies, have all been in common use for detection of disseminated carcinoma cells: the A45-B/B3 protocol (Hamburg), the CK2 protocol (Augsburg) and the AE1AE3 protocol (Oslo). For all protocols, the immunostained cells were visualized by the same alkaline-phosphatase (AP) detection system (APAAP) followed by detection of the cells by manual screening and by two different automated screening systems (ACIS from Chromavision and MDS1 from Applied Imaging). Detected AP-visualized cells were morphologically classified into unambiguous hematopoietic (Uhc) and questionable cells (Qc, potentially interpreted as tumor cells). RESULTS: Seven of 48 BMs (15%) harbored > or = 1 AP-visualized cell(s) among 1 x 10(6) BM MNC, both for the A45-B/B3- and for the AE1AE3 protocol, while for CK2 a higher proportion of BMs (21 BMs; 44%) harbored AP-visualized cells (P < 0.01, McNemar's test). The number of Qc was, for all protocols, 1 log lower than the total number of AP-visualized cells. On average, the frequency of Qc was 0.04, 0.08, and 0.02 per 10(6) BM MNC with A45-B/B3, CK2 and AE1AE3, respectively, and the number of Qc-positive BMs 1, 4, and 1. The MDS1 screening sensitivity was similar to manual screening, while ACIS detected fewer cells (P < 0.001, McNemar's test). CONCLUSIONS: All protocols resulted in AP-visualization of occasional hematopoietic cells. However, morphological classification brings the specificity to a satisfactory high level. Approximately 10% of AP-visualized cells were categorized "questionable". The CK2 protocol turned out less specific than the A45-B/B3 and AE1AE3 protocols.
Subject(s)
Bone Marrow Cells/cytology , Bone Marrow Cells/immunology , Clinical Laboratory Techniques/standards , Epithelial Cells/cytology , Adult , Alkaline Phosphatase/analysis , Autoanalysis/standards , Bone Marrow Examination/methods , Bone Marrow Examination/standards , Epithelial Cells/immunology , Europe , Female , Humans , Immunohistochemistry , Male , Reference Values , Sensitivity and SpecificitySubject(s)
Eosinophilia/complications , Myeloproliferative Disorders/complications , Receptor, Platelet-Derived Growth Factor alpha/genetics , mRNA Cleavage and Polyadenylation Factors/genetics , Aged , Blast Crisis/blood , Chronic Disease , Eosinophilia/blood , Eosinophilia/pathology , Humans , Leukocyte Count , Male , Myeloproliferative Disorders/blood , Myeloproliferative Disorders/pathology , Oncogene Proteins, Fusion/genetics , Platelet CountABSTRACT
BACKGROUND: Patients with follicular (FL) or mantle cell lymphoma (MCL) are incurable with conventional therapy. We investigated the safety and efficacy of rituximab consolidation after autologous stem cell transplantation (ASCT) in order to prevent relapse by clearance of minimal residual disease (MRD). METHODS: Rituximab was given approximately 8 weeks after CD34+ cell enriched ASCT at 375 mg/m2, weekly for 4 weeks. Monitoring of MRD was performed by repetitive PCR analyses. RESULTS: Thirty-one patients were included; one died early after ASCT before rituximab administration. Thirty patients (20 FL, 10 MCL) were evaluable after rituximab consolidation, and 27 of these were assessable for MRD detection. Rituximab consolidation post-ASCT was safe, the most common toxicity being infection. At a median follow-up of 42 months (range 13-96) after ASCT, 25 patients were censored with an actuarial event-free survival (EFS) of 81% at 4 and 5 years. Four patients (two FL, two MCL) relapsed, and one additional MCL patient died unexpectedly in complete remission. PCR-negativity was observed in 22% of the patients before ASCT, 53% post-ASCT (P=0.0547), 72% after rituximab (P=0.0018) and 100% at 6 months post-transplant (P < 0.001). CONCLUSIONS: One single course of rituximab consolidation given after ASCT is safe, may help to eliminate MRD and may translate into improved EFS in both FL and MCL patients.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Infections/chemically induced , Leukopenia/chemically induced , Lymphoma, Follicular/therapy , Lymphoma, Mantle-Cell/therapy , Male , Middle Aged , Neoplasm Staging , Peripheral Blood Stem Cell Transplantation , Postoperative Care , Rituximab , Survival Analysis , Transplantation, Autologous , Treatment OutcomeABSTRACT
We treated 305 de novo acute myeloid leukemia (AML) patients aged =60 years with risk-adapted therapy. Patients with CBF leukemias or normal karyotype and good response to induction I [=5% bone marrow (BM) blasts on day 15] were considered standard risk (SR), all others as high risk (HR). Patients with t(15;17) were excluded. Chemotherapy comprised double induction followed by early consolidation. As late consolidation, SR patients received high-dose cytarabine/daunorubicin (AraC/DNR). SR patients with normal karyotype were allotransplanted from HLA-matched siblings. HR patients were allotransplanted or if no sibling donor was available autotransplanted with peripheral blood progenitor cells (PBSC) harvested after early consolidation. 89% of the SR and 60% of the HR patients achieved CR. The continuous complete remission (CCR) rate at 80 months (median follow-up: 48 months) was 48% for SR and 32% for HR. The CCR rate was 54% for t(8;21), 47% for normal karyotype, and 33% for inv(16) patients. In the HR group, the CCR rate did not differ significantly for patients with bad response to IVA-I, unfavorable karyotype, or both. Forty-five HR patients were autotransplanted (n=20) or allotransplanted (n=25). The probability of CCR was 44% for autotransplantation vs 33% for allotransplantation. In conclusion, our risk-adapted strategy produced encouraging results in SR patients. Early response to therapy is a strong prognostic factor that predicts the probability of CR and long-term outcome.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/therapy , Stem Cell Transplantation , Adolescent , Adult , Amsacrine/administration & dosage , Amsacrine/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Cytarabine/administration & dosage , Cytarabine/adverse effects , Daunorubicin/administration & dosage , Daunorubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Idarubicin/administration & dosage , Idarubicin/adverse effects , Karyotyping , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Prognosis , Prospective Studies , Remission Induction , Risk Assessment , Survival AnalysisABSTRACT
The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32-60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade >I in 75% of patients. Three patients developed reversible veno-occlusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Bone Marrow/radiation effects , Busulfan/administration & dosage , Cyclophosphamide/administration & dosage , Female , Humans , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/mortality , Peripheral Blood Stem Cell Transplantation/adverse effects , Peripheral Blood Stem Cell Transplantation/mortality , Radiotherapy, Adjuvant/methods , Remission Induction/methods , Survival Analysis , Transplantation Conditioning/adverse effects , Transplantation, Autologous , Treatment OutcomeABSTRACT
Among the various immunotherapeutic approaches, monoclonal antibodies in particular have acquired clinical relevance. In patients with non-Hodgkin's lymphoma and in breast cancer it has been shown that antibody therapy and chemotherapy are not rival forms of treatment, but that the best clinical response is obtained with a combination of the two. Cellular immunotherapy with lymphokine-activated killer cells, tumor-infiltrating lymphocytes, allogeneic T-cells and dendritic cells is still in the experimental stage. This is also true of therapeutic vaccination with tumor antigens. The best clinical results of treatment with antibodies or immunotherapy may be expected in patients with minimal residual disease.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/therapy , Antibodies, Monoclonal/immunology , Antibody Specificity/immunology , Humans , Immunotherapy, Active , Immunotherapy, Adoptive , Neoplasms/immunology , Treatment OutcomeSubject(s)
Antibodies, Monoclonal/therapeutic use , Antigens, Neoplasm/immunology , Neoplasms/drug therapy , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal, Murine-Derived , Clinical Trials as Topic , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/immunology , Epithelium/immunology , Humans , Neoplasms/immunology , Treatment OutcomeABSTRACT
PURPOSE: Previous investigations have shown that cytokeratin 18 positive bone marrow cells in localized and lymphatically spread prostate cancer correlates with neither established prognostic factors nor with the biochemical and clinical course after radical prostatectomy. Since the well-known down-regulation of cytokeratin 18 in tumor cells may lead to false-negative results, we asked whether staining with a pan-cytokeratin antibody recognizing a common epitope of cytokeratins 8, 18 and 19 would result in different data. MATERIALS AND METHODS: Preoperative bone marrow aspirates of 82 patients with localized (N0) and lymphatically spread (N1) prostate cancer were examined using the monoclonal antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45. RESULTS: In contrast to findings with the cytokeratin 18 antibody, those with the pan-cytokeratin antibody correlated with the biochemical course. At a median followup of 1,477 days (4 years) patients with pan-cytokeratin positive cells in the preoperative bone marrow aspirate had biochemical progression significantly earlier than those with pan-cytokeratin negative results (mean time to prostate specific antigen relapse 886 versus 1,409 days, p < or =0.004). Compared with other parameters, such as prostate specific antigen, pathological stage and Gleason score, preoperative pan-cytokeratin findings proved to be an independent prognostic factor. CONCLUSIONS: Cytokeratin positive cells in the bone marrow also have prognostic relevance in prostate cancer. The comprehensive analysis of these cells, studies of the individual course of these findings and sufficiently long followup allow us to discuss whether and under what conditions metastasis may develop from 1 or several cytokeratin positive cells.
Subject(s)
Bone Marrow Cells/chemistry , Keratins/analysis , Prostatic Neoplasms/chemistry , Adult , Aged , Disease-Free Survival , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Regression AnalysisABSTRACT
Occult hematogenous micrometastases are the major cause for metastatic relapse and cancer-related death in patients with operable primary breast cancer. Although sensitive immunocytochemical and molecular methods allow detection of individual breast cancer cells in bone marrow (BM), a major site of metastatic relapse, current detection techniques cannot discriminate between nonviable shed tumor cells and seminal metastatic cells. To address this problem, we analyzed the relevance of erbB2 overexpression on disseminated cytokeratin-18-positive breast cancer cells in the BM of 52 patients with locoregionally restricted primary breast cancer using immunocytochemical double labeling with monoclonal antibody 9G6 to the p185erbB2 oncoprotein. Expression of p185erbB2 on BM micrometastases was detected in 31 of 52 (60%) patients independent of established risk factors such as lymph node involvement, primary tumor size, differentiation grade, or expression of p185erbB2 on primary tumor cells. After a median follow-up of 64 months, patients with p185erbB2-positive BM micrometastases had developed fatal metastatic relapses more frequently than patients with p185erbB2-negative micrometastases (21 versus 7 events; P = 0.032). In multivariate analysis, the presence of p185erbB2-positive micrometastases was an independent prognostic factor with a hazard ratio of 2.78 (95% confidence interval, 1.11-6.96) for overall survival (P = 0.029). We therefore conclude that erbB2 overexpression characterizes a clinically relevant subset of breast cancer micrometastases.
Subject(s)
Bone Marrow Neoplasms/metabolism , Bone Marrow Neoplasms/secondary , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Receptor, ErbB-2/biosynthesis , Bone Marrow Neoplasms/pathology , Female , Follow-Up Studies , Humans , Immunohistochemistry , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Survival RateSubject(s)
Bone Neoplasms/secondary , Heart Atria , Heart Neoplasms/diagnosis , Hemangiosarcoma/secondary , Hemoptysis/etiology , Kidney Transplantation , Postoperative Complications/diagnosis , Ribs , Thoracic Neoplasms/secondary , Aged , Biopsy , Bone Neoplasms/diagnosis , Bone Neoplasms/immunology , Bone Neoplasms/pathology , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Diagnosis, Differential , Diagnostic Imaging , Heart Atria/immunology , Heart Atria/pathology , Heart Neoplasms/immunology , Heart Neoplasms/pathology , Hemangiosarcoma/diagnosis , Hemangiosarcoma/immunology , Hemangiosarcoma/pathology , Hemoptysis/pathology , Humans , Immune Tolerance/drug effects , Immune Tolerance/immunology , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Postoperative Complications/immunology , Postoperative Complications/pathology , Prednisone/adverse effects , Prednisone/therapeutic use , Ribs/immunology , Ribs/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/immunology , Thoracic Neoplasms/pathologyABSTRACT
The objective of this study was to evaluate the sensitivity and specificity of percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. In a 1-year period 158 image-guided percutaneous core-needle biopsies of enlarged lymph nodes were performed on 149 consecutive patients using a Tru-cut needle fired by a biopsy gun. In 135 cases the biopsy findings could be confirmed by histologic examination of additional tissue samples (n = 59) or by correlation with the patient's clinical and radiologic course (n = 76). The final diagnoses were malignant lymphoma in 65 cases, leukemic nodal infiltration in 2, nodal metastases from a solid tumor in 37 and benign changes or no evidence of malignancy in 31 cases. The core-needle biopsies correctly diagnosed 58 of 65 malignant lymphomas, corresponding to a sensitivity of 89% and a specificity of 97%. Fifty-five of the 58 (95%) correctly diagnosed malignant lymphomas could be subclassified on the basis of the core-needle biopsy. Image-guided core-needle biopsy of enlarged lymph nodes with a Tru-cut needle is a useful method for the diagnosis and subclassification of malignant lymphomas.