Adherence to prophylaxis and quality of life in children and adolescents with severe haemophilia A.

Treatment adherence in adolescents with chronic diseases is around 50%, and failure is more common in preventive therapy. In haemophilia, contradictory results are reported by the published studies. The objective of this study was to evaluate adherence with factor VIII (FVIII) prophylaxis in Spanish patients with severe haemophilia A between age 6 and 20 years. Data were collected retrosp-ectively in the previous 2 years. The primary endpoint was the absolute adherence index (AAI), and the endpoints were related to clinical status, age, prophylaxis regimen, responsibility for factor administration and quality of life (QoL), assessed by the Haemo-QoL questionnaires. A total of 78 patients from 14 Spanish hospitals were recruited. Adherence ranged between -64.4 and 66.7 (mean -3.08). No differences were observed between children and adolescents (7.11 vs. 6.39; P = 0.809). A statistically significant association (P < 0.010) between infra adherent group and target joint was found, as was a statistically significant difference (P < 0.010) between the number of bleeding episodes experienced by the adherent group (mean 1.4) and by infra adherents (mean 4.5). There was no significant difference between AAI and prophylactic regimen (6.35 vs. 6.96, P = 0.848), neither between AAI and the person responsible for factor administration (5.57 vs. 8.79, P = 0.326). The Haemo-QoL scores (8-12 years) were related to adherence level (P < 0.05). Adherence was approximately ideal and patients perceived a high QoL. Because of the repercussions for compliance, it is essential to work during puberty on emotional and self-acceptance aspects of the disease, as well as coping, and the patient's family, school and health team relationships.

Pharmacokinetics and safety of plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency.

UNLABELLED: Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for life-threatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg(-1) on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥ 5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supra-therapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg(-1) every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/ct2/show/NCT00883090.

A novel, fully automated, observer-independent program for semiquantifying striatal ¹²³I-FP-CIT uptake.

OBJECTIVE: To describe and validate a novel, fully automated program specifically designed for the semiquantification of striatal (123)I-FP-CIT uptake using volumes of interest (VOI) analysis. MATERIAL AND METHODS: The proposed algorithm is based on a template that mimics the striatal (123)I-FP-CIT uptake in a healthy subjects, derived from defined anatomical VOIs available from WFU PickAtlas. Four SPECT studies of the anthropomorphic Alderson phantom filled with variable radioactive concentrations were acquired for the experimental validation. Experimental SPECT images were spatially normalized with respect to the previously created template. The binary VOIs corresponding to left caudate and putamen and right caudate and putamen, which were used to construct the template, were projected onto the experimental images to obtain the counts for these regions. To minimize the partial volume effect, a percentage of the voxels in these regions (threshold), rather than all of them, was used. A binary occipital VOI was used to quantify the non-specific uptake. Experimental binding potentials (BPs) were calculated from the counts in these regions. True BPs were calculated from aliquots taken from the solutions used to fill the phantom. RESULTS: There were statistically significant differences in the experimental BP values (p<0.002) according to the percentage of voxels used. A highly significant correlation was achieved between true and experimental BP values, regardless of the percentage of voxels included for quantification. CONCLUSIONS: Our novel, observer-independent program automatically performs the semiquantification of striatal (123)I-FP-CIT uptake in experimental studies.

[Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes]. / La biopsia del ganglio centinela después de quimioterapia neoadyuvante en el cáncer de mama. Relación con los subtipos moleculares.

OBJECTIVE: To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). MATERIAL AND METHODS: A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. RESULTS: SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. CONCLUSIONS: Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC.

Acute venous thrombosis as complication and clue to diagnose a SAPHO syndrome case. A case report.

This report concerns a male adult admitted for sternal and left arm pain, who was diagnosed and treated for acute deep venous thrombosis in the left subclavian and axillary veins. X-ray and a hybrid single photon emission tomography and computed tomography (SPECT-CT) scintigraphy scan revealed high intensity uptake in both sternoclavicular joints, which corresponded to hyperostosis, thereby suggesting a SAPHO syndrome. Upon reviewing the patient's medical history, we found dermatological pustulosis disease and an intermittent sternal chest pain untreated since 10 years ago. In the biochemical study we found erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) elevation, hyperglobulinemia, and mild anaemia. Initial treatment included nonsteroidal anti-inflammatory drugs (NSAIDs) with low response, which then changed to methotrexate, sulfasalazine, and prednisone. The patient's pain was controlled almost completely in 10 months. A control bone scan revealed a marked decrease in intensity of bone deposits according to clinical response. To our knowledge, there are only a few cases of SAPHO and thrombosis and none are followed up with a bone SPECT-CT scan.

[Sentinel node biopsy in T2 breast cancers larger than 3 cm and clinically negative axilla compared with the T1-T2 <3 cm standard indication]. / La biopsia del ganglio centinela en cáncer de mama de más de 3 cm y axila clínicamente negativa frente a la indicación estándar T1-T2 < 3 cm.

OBJECTIVE: To present our experience in the application of sentinel node (SN) biopsy in patients with breast cancer T > 3 cm without clinical evidence of axillary metastasis. MATERIAL AND METHOD: Retrospective study of 393 cases in the period 2001--2006, divided into group (A) 47 patients with 3-5 cm T2N0 tumours and group (B) 346 patients T < 3 cm, N0. We employed the combined technique with 99mTc-colloidal rhenium sulphide and isosulfan blue dye. Preoperative lymphoscintigraphy was performed and the SN was located intraoperatively with a gamma ray detection probe and the blue dye. Axillary lymph node dissection was completed only when the SN was positive for metastasis in the histopathology analysis or not located. RESULTS: The SN detection rate for T2 > 3 cm was 94 % in the scintigraphy and 96 % with the probe, with no statistically significant differences between T < 3 cm (97 % and 98 %). In T2 > 3 cm, the final staging was 45 % pN0, 8 % pN1mi, 34 % pN1a, 11 % pN2a and 2 % pN3a. We found statistically significant differences (p < 0.05) when compared with palpable T < 3 cm and non-palpable cancer (62 % pN0 and 74 % pN0, respectively). In the follow-up of T2 > 3 cm (median 42.88 months) we did not find any axillary relapse which could be considered a false negative of the technique. CONCLUSION: The detection of sentinel lymph nodes is feasible and safe in tumours larger than 3cm with clinically negative axilla. Axillary lymph node dissection can be avoided in 45 % of these patients and therefore, we consider that they should be included as a general indication in breast cancer SN detection.

Staging the axilla with selective sentinel node biopsy in patients with previous excision of non-palpable and palpable breast cancer.

PURPOSE: To present our experience in the therapeutic approach of the sentinel node biopsy (SNB) in patients with previous excision of the breast cancer, divided in non-palpable and palpable lesions, in comparison with time treatment and stagement of breast cancer. METHODS: In the period 2001-2006, 138 patients with prior diagnostic excisional biopsy (96 non-palpable and 42 palpable breast cancer) and 328 without previous surgery (32 non-palpable; 296 palpable cancer) were treated. The combined technique ((99m)Tc-colloidal rhenium and isosulfan blue dye) was the approach for sentinel lymph node (SLN) detection. Axillary lymph node dissection (ALND) was completed only when the SLN was positive for metastasis or not located. RESULTS: Detection rate, if there was prior surgery, was 95% for non-palpable and 98% for palpable cancer, and 99% for one-time treatment group. Metastasis rate in the SLN was 15% in non-palpable cancer (14/91), significantly smaller than in palpable breast cancer (39% if prior surgery and 37% in one-time surgery). According to tumoral size, ALND metastasis rate was similar for T1 and T2 tumors (43-44%). In the follow-up of the groups with prior diagnostic biopsy or surgery of the breast cancer we have not found any false negative in the axilla. CONCLUSION: The detection of the SLN is also feasible in patients with previous surgery of breast cancer. Because SLN metastasis rates are significantly smaller in non-palpable lesions, the effort in screening programs for early detection of breast cancer and also in improving histopathological confirmation of malignancy with ultrasound or stereotactic guided core biopsies must continue.

[Improvement of the imaging quality by a non-uniform attenuation correction system in cardiac SPECT]. / Mejora de la calidad de imagen mediante un sistema de corrección de atenuación no uniforme en SPECT cardíaco.

A non-uniform attenuation correction system has been purchased recently by the Department of Nuclear Medicine of the University Hospital in Salamanca to be used in a dual-detector Picker Axis gammacamera. This system is based on the generation of an attenuation map from each patient using a transmission scan with and without the patient using two Ba-133 sources. At present, this system is only available for a 102 configuration between the detectors so its use is restricted to cardiac single photon emission computed tomography (SPECT). The aim of this work has been to evaluate improvement of the image quality of this attenuation correction system by doing three different tests (evaluation of the recovery coefficient, activity concentration ratio and attenuation residual error). After analyzing all the tests, the results for the non-uniform attenuation correction system have been favorable compared to the conventional correction method employed in the clinical practice.

Mejora de la calidad de imagen mediante un sistema de correcciónde atenuación no uniforme en SPECT cardíaco / Improvement of the imaging quality by a non-uniform attenuation correction system in cardiac spect

En el Servicio de Medicina Nuclear del Hospital Universitario de Salamanca recientemente se ha adquirido un sistema de corrección de atenuación no uniforme para una gammacámara modelo Picker Axis de doble cabezal el cual se basa en la generación de un mapa de atenuación de cada paciente a través de un scan de transmisión con y sin paciente con dos fuentes de Ba-133. Este sistema sólo está disponible, en la actualidad, para la disposición de los cabezales de la gammacámara en 102° con lo cual su uso está restringido a los estudios de tomografía computerizada de emisión de fotón único (SPECT) cardiaco. El objetivo de este trabajo ha sido el de comprobar la mejora en la calidad de imagen de este sistema de corrección de atenuación a través de tres pruebas distintas (evaluación del coeficiente de recuperación, relación de concentraciones de actividad y error residual de actividad). El resultado ha sido favorable para el sistema de corrección de atenuación no uniforme para esas tres pruebas frente al método convencional de corrección de atenuación utilizado en la práctica clínica (AU)

[Otogenic cerebral abscess: a persistent problem]. / Absceso cerebral otógeno: un problema persistente.

A young man with otitis media and cholesteatoma of the left ear developed secondary cerebral abscess. The clinical debut was non-specific, with headache, mild fever, and mild persistent otalgia in spite of early antibiotic treatment. Studies revealed a cerebral abscess, so ENT surgery in collaboration with the neurosurgery department was decided. This case illustrates that clinical manifestations in such cases can be mild and highlights the need to exclude this type of serious pathology.

Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients.

BACKGROUND: Deoxycoformycin (DCF) has been reported to produce high response rates in patients with hairy cell leukemia (HCL), but to the authors' knowledge data regarding experience with such therapy in a large HCL series are scarce. METHODS: Between 1988-1997, DCF (4 mg/m(2)/day, every 2 weeks) was administered to 80 HCL patients in 32 Spanish institutions. In 35 of 78 evaluable patients DCF was the first-line therapy; the remaining 43 patients had received other therapies. Pretreatment variables influencing the achievement of complete remission (CR) and event free survival were identified by multivariate analyses. RESULTS: The median number of cycles administered was 7 (range, 1-22 cycles). A CR was obtained in 56 patients (72%) and a partial remission was obtained in 13 patients, for an overall response rate of 88%. In the multivariate analysis previous splenectomy and an Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 were the parameters adversely influencing CR achievement. With a median follow-up of 31.2 months (range, 0.4-126.5 months), disease recurrence was observed in 11 of the CR patients, 5 of whom showed a further response to DCF. An ECOG performance status > or = 2 was the only pretreatment variable associated with a shorter event free survival. Seven patients died, four during the treatment period. The actuarial median event free survival was 46 months (95% confidence interval, 22.5-69.5 months), and 48.7% of the 56 patients who achieved a CR were expected to be alive and disease free at 5 years. Hematologic toxicity (marked neutropenia [22 cases], anemia [6 cases], and thrombocytopenia [1 case]) was the main side effect, followed by nausea and emesis (5 cases); 14 patients required hospitalization. CONCLUSIONS: The results of the current study confirm the effectiveness and acceptable toxicity of DCF in the treatment of patients with HCL.

bcl-2 expression in plasma cells from neoplastic gammopathies and reactive plasmacytosis: a comparative study.

BACKGROUND AND OBJECTIVE: bcl-2 oncoprotein plays a major physiological role in hemopoietic and non-hemopoietic cells by preventing apoptosis (programmed cell death). Disregulation of this process may be important in oncogenesis and the response to treatment of patients with different hematological malignancies. We have investigated the levels of bcl-2 expression in plasma cells from patients with reactive plasmacytosis (RP), monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM), correlating the bcl-2 expression and clinico-biological features in MM patients. DESIGN AND METHODS: The percentage of bcl-2 (+) plasma cells and levels of bcl-2 protein expression were investigated in 73 patients at diagnosis. Immunofluorescence and immunoenzymatic methods were applied using McAb against bcl-2 protein, and the intensity of protein expression was assessed by both the mean channel fluorescence intensity (MFI) and semiquantitative methods. To evaluate the intensity of bcl-2 expression in proliferating plasma cells, sequential double immunoenzymatic staining with McAb Ki-67 and bcl-2 was applied in 10 patients with MM. Correlations between bcl-2 expression and the clinico-biological features in MM patients were also studied. RESULTS: The proportion of bcl-2 (+) plasma cells was significantly higher in MGUS and MM than in RP (p < 0.001). The intensity of bcl-2 expression in plasma cells (assessed by MFI) was significantly different between all groups studied (p < 0.0001). RP showed lower expression than MGUS and MM patients. MM stage III patients demonstrated higher bcl-2 expression values than MGUS (p < 0.01). According to the proportion of plasma cells expressing Ki-67, patients with a proliferative index (Ki-67+) > 4% showed lower bcl-2 expression than patients with proliferative index < 4% (p < 0.05). Immunocytochemistry showed that plasma cells from RP had a lower intensity of bcl-2 expression than MM (p < 0.001), and double immunostaining Ki-67/bcl-2 demonstrated that the majority of proliferating plasma cells had weak bcl-2 expression. There was no correlation between bcl-2 expression and clinico-biological parameters, response to therapy or overall survival in MM patients. INTERPRETATION AND CONCLUSIONS: Globally, the number of bcl-2 (+) plasma cells and the intensity of protein expression in neoplastic gammopathies are significantly higher than in reactive plasmacytosis and bcl-2 levels tend to increase with disease stage. bcl-2 may be relevant to the pathogenesis of malignant gammopathies, prolonging the survival of plasma cells by preventing apoptosis and increasing the chance of acquiring additional gene defects. bcl-2 expression could also contribute to the resistance to chemotherapy observed in MM disease.

Low bone density with normal bone turnover in ovariectomized and streptozotocin-induced diabetic rats.

Diabetes and estrogen deficit are known causes of osteopenia, diabetes being associated with a low bone turnover and estrogen deficit with a high bone turnover. In the present work, we studied the effect of combined ovariectomy and diabetes on bone mineral content (BMC) and bone mineral density (BMD) and several bone markers in the rat. Four groups of rats were studied: control (C), ovariectomized (O), diabetic (D), and ovariectomized and diabetic (DO). Twelve weeks after starting the experiments, BMC and BMD of the first six lumbar vertebrae were measured; a bone formation marker (BGP) and a bone resorption marker (free collagen cross-links, PYD) were also analyzed. Diabetic rats showed diminished gain in bone mass, BMC (D: 0.417 +/- 0.028 g, DO: 0.422 +/- 0.020 g) and BMDs (D: 0.171 +/- 0.006 g/cm2, DO: 0.174 +/- 0.006 g/cm2) both being significantly (P < 0.001) lower than those of control (C: BMC 0.727 +/- 0.024 g and BMD 0.258 +/- 0.004 g/cm2) and ovariectomized (O: BMC 0.640 +/- 0.044 g and BMD 0.240 +/- 0.009 g/cm2) groups. Moreover, the BMC and BMD of the C group were significantly (P < 0.05) higher than that of the O group. BGP and PYD levels were significantly (P < 0.01) higher in the O group (BGP: 138.2 +/- 16.8 ng/ml, PYD: 270.2 +/- 17.8 nM/mM) than those found in the control rats (BGP: 44.7 +/- 4.8 ng/ml, PYD: 165.6 +/- 12.5 nM/mM); the D group showed significantly (P < 0.01) lower values (BGP: 27.4 +/- 14.6 ng/ml, PYD: 55.0 +/- 7.4 nM/mM) than those of the control group. The DO group showed similar levels (BGP: 43.4 +/- 5.1 ng/ml, PYD: 146.7 +/- 14.6 nM/mM) to those found in the C group. Although bone marker levels in the O and D groups were in accordance with those expected in these situations, in the DO group the corresponding levels are apparently "normal." Also, the decrease of gain in bone mass observed after combining estrogen deficit and diabetes (DO group) did not seem to be more marked than that caused by diabetes alone.

[Relation between the Toynbee phenomenon and tube dysfunction]. / Relación del fenómeno de Toynbee con la disfunción tubárica.

The effect of the Toynbee phenomenon in patients with nasal packing was studied. Nasal packing was used in 35 patients admitted for surgical correction of septal deviation. Middle ear pressure was measured during nasal packing and the results were compared with nasopharyngeal pressure gradients recorded during the Toynbee maneuver. The aim of the study was to demonstrate that one of the main causes of tube dysfunction during nasal obstruction is the Toynbee phenomenon.

[The Toynbee's phenomenon effect on the middle ear during nasal tamponade]. / Efecto del fenómeno de toynbee en el oído medio durante el taponamiento nasal.

Is has been demonstrated by some AA. that nasal packing can cause Eustachian tube dysfunction. There are several motives, isolated or united as well, that have been offered to account for Eustachian tube dysfunction, but the exact causative mechanism still remains unclear. We have studied the Eustachian tube function in 75 patients with septal deviation that underwent septal surgery followed by anterior nasal packing. The aim of our work is to demonstrate that one of the main causes of the tubal dysfunction, after bilateral packing of nasal cavities, is the Toynbee's phenomenon.

Deletion of exon b3 of the BCR gene in CML: easy breakpoint mapping by a two-round PCR.

We have performed the molecular analysis for the detection of the BCR-ABL and ABL-BCR fusion genes in 50 patients with myeloproliferative disorders. All patients diagnosed with CML (13 out of 50) were positive for the BCR-ABL hybrid. Six CML patients (46%) showed ABL-BCR amplifications of the Ib-BCR type. All rearrangements but one were concordant. The aberrant case presented a deletion of exon b3, in addition to the alternative Ib-BCR and Ia-BCR. Its possible origin and relevance are briefly discussed.

[Combined treatment with factor VIII and immunosuppressive agents in a young woman with acquired factor VIII inhibitor]. / Tratamiento combinado con factor VIII e inmunosupresores en mujer joven con inhibidor adquirido del factor VIII.

A twenty seven year-old woman is reported with severe haemorrhagic symptoms caused by an acquired coagulant factor VIII inhibitor eleven months after delivery. The inhibitor was quantified as 77 units according to the Bethesda method. Steroids treatment and high-dose immunoglobulins failed to elicit any response. Combined chemotherapy will cyclophosphamide, vincristine and prednisone after intravenous factor VIII, every fourth week, succeeded in eradicating the acquired inhibitor and progressively restoring the rates of factor VIII in this patient with acquired haemophilia.

Donor leukocyte infusions for treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation.

A 24-year-old man with acute myelomonocytic leukemia (AML-M4) who relapsed 6 months after an allogeneic BMT was treated with chemotherapy followed by donor leukocyte infusions (4.19 x 10(8) mononuclear cells/kg). The patient developed grade II acute GVHD that responded to therapy with CsA and prednisone. Chimerism was assessed by PCR amplification of the MCT 118 hypervariable region. Fourteen months after donor leukocyte infusions the patient remains in complete remission, without any morphologic and cytogenetic evidence of leukemia, and with a complete donor chimerism. This case shows that donor leukocyte infusions are an effective therapy for some acute myeloid leukemia patients who relapse after allogeneic BMT.

BCR-ABL rearrangement and 'variant' Philadelphia chromosome in de novo acute myelogenous leukaemia FAB subtype M1.

We report a case of de novo acute myelogenous leukaemia FAB subtype M1 that presents a cytogenetic complex translocation between chromosomes 7, 9 and 22, producing a 'variant' Philadelphia chromosome. Molecular analysis revealed a BCR-ABL rearrangement involving exons b3 and a2 (b3a2). Haematological parameters and genetic analysis again raise the problem of the true nature of this disease, which is briefly discussed.

Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.

AIMS: To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease. METHODS: Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells. RESULTS: The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage. CONCLUSIONS: Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.