SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis.

The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression-and consequently, H3K36 trimethylation-was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

Longitudinal Evaluation of Bone Mineral Density and Bone Metabolism Markers in Patients with Indolent Systemic Mastocytosis Without Osteoporosis.

Systemic Mastocytosis has been long identified as a potential cause of osteoporosis; nevertheless, data regarding longitudinal variation of bone mineral density (BMD) in patients with indolent systemic mastocytosis (ISM) are missing . We studied BMD variation at lumbar spine and proximal hip after 30-month (±6 months) follow-up in a large cohort of patients (83) with ISM without osteoporosis, supplementated with vitamin D and/or calcium when needed. We also analyzed the correlation between variation of BMD, basal serum tryptase levels and bone turnover markers (BTM). Sixty-four percent of our population was male; mean age was 52.1 (±11.5) years. Vitamin D insufficiency (serum levels of 25-OH-vitamin D, 25OHD, lower than 75 nmol/L) was found in more than 70 % of patients. After a follow-up of 30 ± 6 months with only vitamin D (5000-7500 IU weekly of oral cholecalciferol) or calcium (500 mg/die) supplementation when needed, we observed 2.1 % increase in BMD at lumbar spine, with no significant changes at hip. At the end of follow-up, almost 60 % of patients showed 25OHD serum levels still lower than recommended, despite vitamin D supplementation. Reduction in BMD after follow-up significantly correlated with high C-telopeptide of type I collagen serum levels at the time of diagnosis. In patients with ISM without osteoporosis, a routinary BMD evaluation within a time <2 years is not justified, except in the presence of elevated BTM. In these patients, vitamin D supplementation is frequently needed.

Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis.

Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy.

Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper.

Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation.

Mastocytosis and allergic diseases.

Mastocytosis is a clonal disorder characterized by proliferation and accumulation of mast cells in various tissues, mainly skin and bone marrow. It can cause a wide variety of clinical manifestations-other than urticaria pigmentosa-that can lead to inappropriate release of mediators by mast cells. The most severe manifestation is anaphylaxis. The triggers of anaphylaxis in adults with mastocytosis are numerous, but Hymenoptera stings seem to be the most frequent, followed by foods and drugs. Therefore, to prevent severe reactions, it is very important to recognize and avoid potential triggers; in addition, venom-allergic patients must receive lifelong immunotherapy, which has proven very effective. Given that published data on drug anaphylaxis in patients with mast cell disorders are scarce, it is not currently possible to provide clear recommendations. The risk of systemic reactions during general anesthesia can be reduced by assessing risk on an individual basis (previous reaction to a drug or reaction during surgery) and by avoiding specific trigger factors (patient temperature changes, infusion of cold solution, tissue trauma, friction, and other mechanical factors).

Validation of a stoma-specific quality of life questionnaire in a sample of patients with colostomy or ileostomy.

AIM: The aim of this study was to determine how socio-demographic and clinical variables affect quality of life (QoL) and to assess the validity of a 20-item scale in a sample of Italian subjects with colostomy, ileostomy and multiple stomata. METHOD: A cross-sectional multicentre survey was carried out in Italy between 2009 and 2010 in 73 stoma centres coordinated by the University of Padova. Patients aged 18 years old and above with a history of nontemporary stoma were included in the study. The Stoma Care QoL scale was measured and validated using a Rasch model. Socio-demographic and clinical characteristics were considered in the analyses. RESULTS: Two hundred and fifty-one patients were recruited for the study; the mean age was 62 years, 58% were men, 72% had colostomy and 25% ileostomy; approximately 70% of patients had intestinal cancer requiring a stoma, 13% a complication and 10% an inflammatory disease. No significant differences were observed throughout strata in the Stoma Care QoL scale index, except for geographical area, where subjects from south Italy showed a significantly lower index than subjects living in other parts of Italy (P < 0.01). Colostomy and ileostomy patients reported very similar QoL. Cronbach's alpha for the Stoma Care QoL scale was 0.90 (95% CI 0.88-0.92). Rasch analysis supported the viability of the Stoma Care QoL scale questionnaire and showed acceptable goodness-of-fit. Three under-fitted items were observed. CONCLUSION: The study confirms the validity of the 20-item Stoma Care QoL scale questionnaire as a research tool for stoma patients but the number of items could be reduced.

The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting.

BACKGROUND: Systemic mastocytosis (SM) may be associated with hymenoptera allergy. In such cases, immunotherapy is a life-saving treatment, but a circumstantiated diagnosis is needed for its prescription. Patients with SM and previous reactions to stings, but with negative tests represent a diagnostic dilemma. The basophil activation test (BAT) may be helpful in refining the diagnosis. OBJECTIVE: We assessed the usefulness of BAT in subpopulations of mastocytosis patients, including those with negative tests for insect allergy. METHODS: Within a population of patients with mastocytosis and previous stings, we studied by BAT and augmented intradermal test (IDT) (10 µg/ml) two groups: (1) with reactions to stings and negative tests; (2) without reactions and negative tests. Basophil activation test was performed with different venoms, assessing at flow cytometry basophils' activation. RESULTS: Sixty-three patients had mastocytosis and 52 had reactions to previous hymenoptera stings. Of them, seven proved negative to diagnostic tests. In six of seven of those patients, BAT was negative with all venoms, and in one, basophils resulted activated also with the negative control. In six patients without previous reactions and negative tests, BAT was totally negative in five of six patients and weakly positive to Hornet in one. Finally, the IDT at 10 µg/ml venom produced nonspecific positive results in most cases. CONCLUSION: In patients with mastocytosis, the negative results of standard tests are reliable, because BAT and IDT at higher concentration do not add useful information.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor.

Zeta-associated protein-70 (ZAP-70), mostly assessed by flow-cytometry (FC), recently emerged as reliable prognostic factor in chronic lymphocytic leukaemia (CLL) at presentation. We evaluated ZAP-70 expression in 156 CLL patients by immunohistochemistry (IHC) on formalin-fixed bone marrow (BM) biopsies at diagnosis. At presentation, 117 patients (75%) were with Binet stage A, 27 (17%) stage B and 12 (8%) stage C. Median follow-up was 61 months (range 6-242). ZAP-70 was expressed in neoplastic lymphocytes of 69 patients (44%). Concordance between ZAP-70 by IHC and ZAP-70 by FC, immunoglobulin heavy chain variable genes (IGHV) mutational status and CD38 expression was found in 41/46 (89%), 41/49 (80%) and in 60/88 (68%) tested cases, respectively. ZAP-70 expression significantly correlated with advanced Binet stage (B-C), diffuse BM infiltration, increased lactate dehydrogenase (LDH) and beta2-microglobulin serum levels and lymphocyte doubling time <12 months. ZAP-70 positivity was significantly related to poorer time to progression (median 16 months vs 158 of ZAP-70-negative cases) (P<0.0001) and overall survival (median 106 months vs not reached) (P=0.0002); this correlation was confirmed at multivariate analysis. ZAP-70 expression correlated with poorer outcome also when evaluated only in the 117 stage A patients. In conclusion, immunohistological detection of ZAP-70 on formalin-fixed BM biopsies at diagnosis appears a useful methodological approach to identify patients with poor prognosis in CLL.

Restauración de la audición con prótesis implantables. B.A.H.A., implante coclear e implante auditivo de tronco cerebral / Restoration of hearing with implantable prosthesis

The authors' present an experience with restoration of hearing with implantable prothesis

Serum levels of soluble CD30 improve International Prognostic Score in predicting the outcome of advanced Hodgkin's lymphoma.

BACKGROUND: The International Prognostic Score (IPS) and circulating levels of the soluble form of CD30 molecule (sCD30) have both been associated with poor outcome in patients with advanced Hodgkin's lymphoma (HL). The aim of this study was to assess the prognostic power of the combined evaluation of sCD30 and IPS in these patients. PATIENTS AND METHODS: We included 101 patients with advanced HL, treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or MOPP (mechlorethamine, vincristine, procarbazine and prednisone)/ABVD chemotherapy with or without radiotherapy. All were tested for pre-treatment sCD30 levels. RESULTS: Six-year estimated overall survival (OS) and failure-free survival (FFS) was 89% +/- 3% and 75% +/- 4%, respectively. Thirty-three patients (33%) had IPS >2; their FFS was 60% compared with 82% in the remaining patients (P = 0.027). Serum sCD30 levels were > or =100 U/ml in 41 (41%) patients; their FFS at 6 years was 58%, compared with 87% in patients with sCD30 <100 U/ml (P = 0.003). In the 18 patients with both sCD30 > or =100 U/ml and IPS >2, FFS was significantly worse (44%) than in patients with low sCD30 and low IPS (89%) (P <0.001) or with only one of the two adverse prognostic factors (73%) (P = 0.03). CONCLUSIONS: In our study, the combination of IPS >2 and serum sCD30 levels > or =100 U/ml identifies a sizeable subgroup (18%) of advanced HL patients with very poor FFS, who might take advantage of intensified up-front treatment strategies.

Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin.

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25; Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38-100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

Arthroscopic capsular release for the stiff shoulder. Description of technique and anatomic considerations.

The anatomic proximity of several neurovascular structures remains a major concern to the surgeon interested in performing arthroscopic capsular release. We evaluated the anatomic relationships between the released capsule and the axillary nerve, posterior circumflex humeral artery, and brachial artery in a frozen cadaveric model. With the aid of electrocautery, seven cadaveric shoulders underwent complete arthroscopic capsular release. The release was performed circumferentially, approximately 1 cm lateral to the glenoid rim. All shoulders were subsequently frozen and sectioned through the plane of the capsular release while the shoulder was maintained in the lateral arthroscopic position (45 degrees of abduction and 20 degrees of flexion). Anatomic dissection revealed an average distance from the capsular release to the axillary nerve of 7.04 mm (95% confidence interval, 5.62, 8.47), to the posterior circumflex humeral artery of 8.2 mm (95% confidence interval, 6.41, 9.99), and to the brachial artery of 15.97 mm (95% confidence interval, 9.85, 22.09). As the axillary nerve was followed medially from the released capsule, the inferior border of the subscapularis muscle became interposed between the capsule and the axillary nerve. This limited anatomic study shows that a relatively safe margin between the capsule and the neighboring neurovascular structures can be obtained by releasing the capsule within 1 cm of the glenoid rim.

Intra-articular fractures of the distal end of the radius treated with an adjustable fixator system.

Twenty-five wrists with comminuted, displaced, intra-articular fractures of the distal radius were prospectively treated with an adjustable external fixator for an average of 51 days. Twenty fractures (80% [20 of 25] were available for follow-up) in 16 adults (mean age, 34 years) were treated with the Wrist Jack external fixator system (Hand Biomechanics Lab, Sacramento, CA) and evaluated at a mean follow-up period of 25 months. Ten patients (12 fractures) sustained high-energy trauma with multiple injuries, while 6 patients (8 fractures) sustained isolated distal radius fractures. Percutaneous pins supplemented the fixation in 6 fractures. All fractures were reduced to restore articular congruity to within 1 mm. At follow-up, 5% were excellent, 75% good, 20% fair, and none as poor using the demerit point system of Gartland and Werley as modified by Sarmiento. Grip strength averaged 80% of the unaffected limb. Seventeen of the 20 fractures showed some evidence of articular incongruity at follow-up evaluation. Restoration of palmar tilt, radial inclination, radial length, and range of motion were at acceptable values. Subjective analysis confirmed 85% of the patients to have only occasional pain or none at all and 15% to have some pain with weakness or limitation of motion. Two patients required additional surgery: 1 underwent a Darrach procedure and the other a tendon transfer for a rupture of the extensor pollicis longus tendon. Results suggest that an external fixator system provides an additional alternative to the surgical armamentarium for an otherwise difficult fracture fixation problem.

The low incidence of suprascapular nerve injury after primary repair of massive rotator cuff tears.

We measured the incidence of cuff retear and injury to the suprascapular nerve after mobilization and repair of a massive rotator cuff tear. Of one hundred four rotator cuff repairs performed over a 5-year period, 10 patients (7 men and 3 women, age range 22 to 68 years) had primary repairs of massive rotator cuff tears requiring cuff mobilization and an acromioplasty as their only procedure. These patients were evaluated at a mean of 2.5 years (range 2.0 to 3.0 years) after surgery. At follow-up electromyographic examination confirmed that 1 of the 10 patients had an iatrogenic suprascapular nerve injury, whereas ultrasound evaluation revealed that 2 of 10 repairs failed. Pain relief was achieved in the eight patients with intact repairs and not in the two with recurrent tears. All patients had some limitation of active motion or strength, especially in external rotation. Thus 7 of 10 patients had neither evidence of nerve injury nor recurrent rotator cuff tears yet still showed limited active motion or weakness. It appears that operative injury to the suprascapular nerve during cuff mobilization can occur, but other factors such as inadequate cuff muscle function are more frequently responsible for the poor functional outcomes seen after successful repairs of massive rotator cuff tears.

Eighty-one percent event-free survival in advanced Burkitt's lymphoma/leukemia: no differences in outcome between pediatric and adult patients treated with the same intensive pediatric protocol.

BACKGROUND: Advanced Burkitt's lymphoma (BL) has an extremely poor prognosis in adults. With a previous protocol including CNS prophylaxis, 40% of our adult patients achieved CR and only 13% became long survivors. In 1988, following this poor experience, we adopted a very intensive pediatric-derived protocol. PATIENTS AND METHODS: Twenty-one consecutive patients, 8 adults (median age 35, stage III: 1; IV: 7; leukemias: 6) and 13 children (median age 10, state III: 8; IV: 5; leukemias: 4) were treated with the same protocol (POG 8617), based on alternate two-phase cycles with sequential high-dose CTX, VCR, ADM + CNS chemoprophylaxis (phase A) and HD MTX + HiDAC (phase B). Adults received 6 cycles, children 8; i.t. prophylaxis in phase B was omitted in adults. RESULTS: Twenty of 21 (95%) patients achieved CR (adults 100%, children 92%). Two patients died early; 2 relapsed at 4 and 9 months. With a median follow-up of 28 months (4-96), 17 patients (81%) are event free (adults 75%, children 85%). Severe infections affected 62% of adults and 15% of children. CONCLUSIONS: (1) The prognosis of adult advanced BL definitely improved with this intensive protocol. (2) There were no differences in outcome between adults and children. (3) Outcome of lymphoma and leukemia was similar. (4) Severe infections occurred frequently in adults. This intensive pediatric protocol requires a careful supportive therapy.

In leukaemic CD5+ B cells the expression of BCL-2 gene family is shifted toward protection from apoptosis.

This study further investigated the mechanisms that control apoptosis in leukaemic CD5+ B cells, and focused on the Bcl-2 gene family. The pattern of expression of Bcl-2, Bcl-xL, Bcl-xS and Bax genes, selected because of their interrelated role in the control of apoptosis, was analysed in a series of CD5+ B-cell chronic lymphoid leukaemias. Cells from 34 patients with chronic lymphoid leukaemia of B-cell type (23 B-chronic lymphocytic leukaemia (B-CLL) and 11 mantle cell lymphoma (MCL) in leukaemic phase) were investigated. High levels of Bcl-2 mRNA were observed by Northern blot and high levels of Bcl-2 protein were detected by cytofluorograph analysis with a specific monoclonal antibody (MAb) in all cases. Strong Bax expression was detected by RT-PCR in 20/23 B-CLL cases; Bax was also observed in 8/11 MCL in leukaemic phase with variable degree of intensity. In both B-CLL and MCL samples the presence of Bax protein was confirmed by cytofluorograph analysis. RT-PCR detected high levels of Bcl-xL in 16/23 B-CLL and in 8/11 MCL in leukaemic phase, whereas Bcl-xS was detectable in low to trace amounts respectively in 13/23 B-CLL and in 6/11 MCL in leukaemic phase. According to the functional role of Bcl-2, Bcl-xL, Bcl-xS and Bax, these data indicate that the pattern of Bcl-2 family genes expression in leukaemic CD5+ B cells is skewed toward prevention of apoptosis and may thus favour the relentless accumulation of CD5+ leukaemic B cells.

Primary extranodal lymphomas of Waldeyer's ring, stage IE and IIE.

We reviewed 45 cases of Waldeyer's ring lymphomas (25 stage IE, 20 IIE): 73% had high-grade histology according to Kiel's classification. Fourteen patients received radiotherapy alone and 31 chemotherapy, combined with radiotherapy in 28. Complete remission rate was 95% and relapse rate 32%. At 8 years overall disease-related survival (DRS) and event-free survival (EFS) were 69% and 57% respectively. Combined treatment provided both significantly better DRS (82% vs 42%) and EFS (76% vs 25%) than radiotherapy alone. Most of the patients with high-grade histology (26/33) received the combined treatment and this subgroup achieved a long-term EFS of 78%. Both DRS and EFS were also significantly longer in patients under 60. At multivariate analysis favorable prognostic factors were lower age for DRS and combined treatment for EFS.

Circulating levels of soluble CD23 reflect clinical and biological features of leukemic B-cell chronic lymphoproliferative disorders.

One hundred and twenty-four sera from patients with various leukemic B-cell chronic lymphoproliferative diseases were investigated at diagnosis by ELISA for their soluble CD23 content. Immunophenotyping was carried out in all patients, and in a selected subset the mean number of membrane-bound CD23 molecules per cell was also investigated. Seventy-three patients had typical B chronic lymphocytic leukemia, 41 leukemic B-cell disorders with atypical morphological and/or immunophenotypic features, 5 had low-grade follicular cell lymphoma in the leukemic phase, and 5 had splenic lymphoma with villous lymphocytes. Soluble CD23 levels were significantly higher than in normal sera (mean +/- SD: typical B chronic lymphocytic leukemia 3,650 +/- 4,654 U/ml, atypical B chronic lymphocytic leukemia 3,440 +/- 4,671 U/ml, follicular cell lymphoma 3,200 +/- 1,511 U/ml, splenic lymphoma with villous lymphocytes 8,236 +/- 7,294 U/ml, controls 137 +/- 128 U/ml; P < 0.001). More advanced Rai's stages were related to higher soluble CD23 levels (P < 0.01), both in typical and atypical B chronic lymphocytic leukemias, the highest levels and the best correlation with the absolute number of circulating CD19+ cells (r = 0.50) being observed in the typical form. The number of membrane-bound CD23 molecules per cell was significantly higher in typical than in atypical B chronic lymphocytic leukemias (mean number 156,727 +/- 94,668 vs. 12,010 +/- 10,643, P < 0.001). Our data suggest that soluble CD23 levels correlate with the clinical and biological features of leukemic B-cell lymphoproliferative disorders.