A six-month audit of the isolation of Fusobacterium necrophorum from patients with sore throat in a district general hospital.

Fusobacterium necrophorum is an obligate anaerobe believed to be a member of the normal flora of the human oropharangeal and urogenital tract. It has been associated with deep-seated infections and was first described in 1936 by Lemierre, a French microbiologist. There is now strong evidence to suggest that it is also a cause of recurrent sore throat and persistent sore throat syndrome (PSTS) without leading to full systemic infection. It is considered to be the second most common cause of sore throat after group A beta-haemolytic streptococci. This study was performed over a six-month period (October 2004 to March 2005) at the Eastbourne District General Hospital. All throat swabs received in the laboratory are cultured routinely for haemolytic group A streptococci and pathogenic Corynebacteria spp. During the study period an extra fastidious anaerobic blood agar plate with neomycin was inoculated, with a 30 microg vancomycin disc placed at the junction of the second and third streaks. This was examined after 48 h for the presence of F. necrophorum. A total of 1157 swabs were processed during the study period: 156 were positive for haemolytic group A streptococci, 57 were positive for F. necrophorum, 47 for group C haemolytic streptococci, nine for group G haemolytic streptococci, and one was positive for C. ulcerans. Patient age ranged from less than a year old to 88. The majority of F. necrophorum isolates were from patients in the 11-25 age group, with an isolation rate of 9.48% (44/464). This age group accounted for 40% (464/1157) of the swabs received during the study period and 77% (44/57) of these were positive for F. necrophorum. Group A haemolytic streptococci showed an overall isolation rate of 13.5%, with peaks of 23% in the 0-10 and 26-35 age ranges. Together, these two organisms were responsible for 18.4% (213/1157) of all throat infections in this study. The results presented here indicate that F. necrophorum is second to group A haemolytic streptococci as a cause of sore throat, especially in the young adult, and introduction of routine culture should be considered.

Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.

PURPOSE: To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS: Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS: The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.

Patterns of outcome following recurrence after myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma.

PURPOSE: To assess the patterns of recurrence, management, and survival following recurrence after myeloablative therapy with autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma (FL). PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with FL received cyclophosphamide and total-body irradiation with ABMT as consolidation of second or subsequent remission. RESULTS: Median length of follow-up was 5 1/2 years, and 33 patients developed recurrent lymphoma a median of 14 months after ABMT. In 26 patients, the recurrence was overt; in seven, it was detected on surveillance investigation. Twenty-six patients presented with recurrence at previous sites of disease. Twenty-two patients (67%) had FL at the time of recurrence; in 11 (33%), there was evidence of transformation to diffuse large B-cell lymphoma. Eight patients were managed expectantly; five were alive 21 to 53 months later. Twenty-five patients have required treatment to date; eight remained alive 6 months to 10 years later, and five were in remission. The Kaplan-Meier estimate of patients alive 5 years after recurrence is 45% (95% confidence interval, 27% to 62%). In univariate and multivariate analyses, survival after recurrence and overall survival after diagnosis were similar to those of a historical control group who received conventional treatment, before the introduction of myeloablative therapy (adjusted hazard ratio [HR], 1.56, P = .3, and HR, 1.34, P = .4, respectively). CONCLUSION: The survival pattern of patients with FL following recurrence after myeloablative therapy and ABMT suggests that this treatment does not compromise outcome in patients in whom it fails, reflecting the survival pattern of the disease when treated conventionally.

Immunocytoma: a retrospective analysis from St Bartholomew's Hospital-1972 to 1996.

PURPOSE: To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. PATIENTS AND METHODS: One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. RESULTS: Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P <. 01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P =.01). A comparison of the three IMC subgroups showed that there was a trend (P =.06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. CONCLUSION: Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.

Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma.

PURPOSE: To assess myeloablative therapy with autologous bone marrow transplantation (ABMT) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival. PATIENTS AND METHODS: Since June 1985, 64 patients with follicular lymphoma have received cyclophosphamide (CY) 60 mg/kg x 2 and total-body irradiation (TBI) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission. The marrow mononuclear cell (MNC) fraction was treated in vitro with three cycles of the monoclonal antibody (MAb) anti-CD20 and baby rabbit complement before cryopreservation. At the time of treatment, 34 patients were in complete remission (CR), and 30 had residual disease present. RESULTS: The median time to engraftment was 28 days (range, 15 to 46) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks, and three patients (excluded from the range) have had delayed recovery (> 6 months) of RBCs and platelets. Fifty two patients are alive; three died as a consequence of the transplant procedure, two died in remission from other causes, and seven died of recurrent lymphoma. There was a significant correlation between survival and the total number of episodes of treatment required during the course of the illness (< or = to three v > three, P = .01). With a median follow-up duration of 3 1/2 years, 35 patients continue in remission between 1 and 8 years, and 24 have developed recurrent lymphoma, five with evidence of transformation to high-grade histology. Freedom from recurrence did not correlate with the time from diagnosis, the number of previous treatments, the presence or absence of residual disease at the time of treatment, or during which specific remission the treatment was given (second v > second). However, comparison with an age-matched, remission-matched, historical control group shows a significant advantage in favor of treatment with CY plus TBI plus ABMT (P = .001); currently, there is no difference in survival. CONCLUSION: These results are encouraging, although preliminary; it remains to be established whether this treatment prolongs survival.

Durable remissions of myelodysplastic syndrome and acute myeloid leukemia after reduced-intensity allografting.

PURPOSE: To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). PATIENTS AND METHODS: Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m2 daily for 5 days and either cyclophosphamide 1 g/m2 daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34+ cells and CD3+ cells infused per kilogram of recipient weight was 4.5 x 106 (range, 1.8 to 7.3 x 106 cells) and 2.9 x 108 (range, 0.1 to 9.6 x 108 cells), respectively. RESULTS: There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [CI], 40% to 86%) and 56% (95% CI, 30% to 68%), respectively. CONCLUSION: This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.

Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma.

PURPOSE: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. RESULTS: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

Detection and significance of bcr-abl mRNA transcripts and fusion proteins in Philadelphia-positive adult acute lymphoblastic leukemia.

Blast cells from an unselected consecutive series of 84 adults presenting with acute lymphoblastic leukemia (ALL) to St Bartholomew's Hospital over a seven year period were tested prospectively by cytogenetic and retrospectively by RT-PCR analysis for the presence of the Ph translocation and bcr-abl mRNA. This combination gave an overall figure of 20.3% for bcr-abl-positive and/or Ph-positive ALL. The incidence of bcr-abl-positive/Ph-positive ALL was most common between the ages of 31 and 50 years, becoming less common after the age of 50. Eight out of ten bcr-abl-positive patients expressed the e1a2 mRNA transcript, the other two expressed the b3a2 and b2a3 transcripts respectively. Cells from all patients with bcr-abl mRNA transcripts expressed the appropriate p190 or p210 bcr-abl protein and all were Ph-positive.

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Human trithorax gene rearrangements in therapy-related acute leukaemia after etoposide treatment.

Molecular analysis of leukaemic blasts from 9 patients with secondary myeloid leukaemia reveals rearrangements of the human trithorax gene (Htrx-1) in three patients, including one in whom abnormalities of chromosome 11 band q23 were not detected by conventional cytogenetics. All three patients had been treated with epipodophyllotoxins, whilst none of the six without rearrangements had received these agents. The patients with rearrangements also presented with different clinical features. These findings support the separation of secondary leukaemia into two classes, and correlate rearrangements of the Htrx-1 gene with a group of secondary leukaemias that follow specific cancer treatment regimens.

Mitoxantrone and cytosine arabinoside as treatment for acute myelogenous leukemia (AML) at first recurrence.

A total of 107 patients with newly diagnosed acute myeloblastic leukemia (AML) were referred to the ICRF Department of Medical Oncology at St Bartholomew's Hospital between August 1986 and July 1989. Of those referred, 92 (87%) were treated with remission induction chemotherapy comprising: Adriamycin, cytosine arabinoside (ara-C) and 6-thioguanine if aged < 60 years (57 patients) or mitoxantrone (MTN) and ara-C if aged > 60 years (35 patients). Of those treated, 54 (58%) entered complete remission (CR). Recurrent AML developed in 38 out of these 54 patients (70%) of whom 25 aged 19-73 years (median 50 years) subsequently received MTN and ara-C as reinduction therapy. The 19 younger patients (under 60 years old) received MTN at 12 mg/m2, intravenously, daily for 5 days and ara-C at 100 mg/m2, intravenously, twice daily for 7 days. The six older patients received the same ara-C schedule but the dose of MTN was reduced to 10 mg/m2 for 5 days. Second CR was achieved in 16 out of 25 patients (64%) [12/19 (63%) and 4/6 (67%) for patients aged under or over 60 years, respectively]. Eight of the patients in whom second CR was achieved were aged under 50 years and were thus eligible for additional consolidation comprising myeloablative therapy with autologous bone marrow transplantation (ABMT). Four patients actually received the latter treatment: two remain in second CR at 21 and 46 months. Three of the remaining eight patients aged > 50 years in whom second CR was achieved remain in second CR 8 to 43 months later. Censored for myeloablative therapy + ABMT, the overall median duration of second CR was 5 months. Although remissions tended to be short, in younger patients the possibility of proceeding to myeloablative therapy with autologous bone marrow support makes the regimen worthwhile and, even in older patients, it was sometimes possible to achieve prolonged second remissions.

Waldenstrom's macroglobulinemia: a retrospective analysis of 40 patients from 1972 to 2001.

From 1972 to 2001 at St. Bartholomew's Hospital 40 untreated Waldenstrom's macroglobulinemia (WM) patients received either chlorambucil (n = 23); cyclophosphamide, vincristine, and prednisolone (CVP) (n = 5); fludarabine-based therapy (n = 5); or other combination chemotherapy (n = 7). Twenty-eight patients (70%) responded to first-line therapy with overall response rates as follows: chlorambucil, 17/23 (74%); CVP, 4/5 (80%); fludarabine-based regimen, 2/5 (40%); other combinations, 5/7 (71%). Twenty patients were treated at progression with chlorambucil, of whom 10 (50%) responded again, 6/13 having had chlorambucil initially, and 4/7 having had other therapy. Although there was a trend towards a survival advantage for patients who responded to chlorambucil, this difference was not statistically significant. At 6 and 11 years, overall survival was 36% v 18% and 15% v 0% for responders and nonresponders, respectively. The overall pattern was the same for patients treated initially with chlorambucil as with other therapy. This retrospective analysis confirms that chlorambucil is an effective first-line agent in WM and has activity when used at subsequent relapse.

Fludarabine in low-grade lymphoma.

During the last 4 years, 88 patients with low-grade non-Hodgkin's lymphoma have received fludarabine, 25 mg/m2 daily for 5 days, repeated every 3 to 4 weeks. Fifty-one patients received fludarabine at recurrence or when the disease was deemed resistant to conventional treatment, 21 patients received the drug in the context of "minimal residual disease" in the hope of complete remission being achieved with a view to proceeding to myeloablative therapy (cyclophosphamide and total body irradiation) with autologous bone marrow transplantation, and 16 newly diagnosed patients received fludarabine as first-line therapy. Myelosuppression was the predominant toxicity, with 55% and 31% of previously treated and newly diagnosed patents, respectively, becoming neutropenic (neutrophils < or = 1.0 X 10(9)/L). The response rate (complete and partial response) was 44% for both patients with recurrent/resistant disease (20 of 45 evaluable patients) and for those with "minimal residual disease" (nine of 20 evaluable patients). In newly diagnosed patients, the response rate was 69% (11 of 16 patients). Five patients died of infection while neutropenic. These results confirm the activity of fludarabine in low-grade non-Hodgkin's lymphoma. Its precise role remains to be determined.

Erythromyeloid lineage fidelity is conserved in erythroleukaemia.

Blast cells from eight patients with erythroleukaemia and one with erythroid blast crisis of chronic myeloid leukaemia were studied for the co-expression of cell surface myeloid and erythroid markers, and the phenotype compared with that of erythroblasts from two patients with megaloblastic anaemia. The technique of dual indirect immunofluorescence was used with a panel of seven mouse monoclonal antibodies against well-defined myeloid antigens (CD11b, 13, 14, 15, 33 and HLA-DR) and a rat antibody, YTH89.1, specific for glycophorin A. No dual fluorescence, emanating from myeloid or erythroid lineage markers, was found to occur in either the neoplastic or non-neoplastic erythroid cells studied. These data support the hypothesis that lineage fidelity is conserved in leukaemia.

ALL masquerading as AUL.

Of 597 cases of acute leukaemia in adults (greater than 16 years) seen at St. Bartholomew's Hospital, London, between May 1973 and January 1982, 412 were diagnosed as AML, 103 as ALL and 58 as Philadelphia chromosome positive blast crisis of CML (13 presenting as acute leukaemia and 45 having a prior chronic phase). The remaining 24 cases were considered to be acute undifferentiated leukaemia. Twenty-one of the latter were investigated using a panel of immunological markers at diagnosis and/or retrospectively using frozen cell suspensions. Eighteen out of 21 were shown to have a predominantly 'lymphoid' phenotype which comprised 12 cases of common ALL (two of whom were Ph1 positive), three cases of null-ALL, one case with a probable early thymic phenotype, and two cases with a monoclonal B lymphoblast phenotype. One 'common ALL' and one 'null-ALL' had a significant proportion of pre-B (cytoplasmic mu chain+) cells. One other case reacted with anti-myeloid sera. Leukaemic blasts from two patients were unreactive with all markers tested. No cases of glycophorin positive erythroleukaemia or anti-platelet (glycoprotein I) positive leukaemia were detected. These observations suggest that the overwhelming majority of acute leukaemias have an identifiable affiliation to the lymphoid or myeloid lineages and that patients diagnosed haematologically as 'AUL' might benefit by therapy appropriate for their leukaemic cell type.

Demonstration of lymphoid antigens in decalcified bone marrow trephines.

A panel of antibodies recognising lymphoid and epithelial antigens in formalin fixed, paraffin embedded sections was applied to a series of 54 bone marrow trephines decalcified by formic or edetic acids. Normal trephines and cases infiltrated by myeloid, lymphoid, and epithelial tumours were included. Patterns of reactivity were distinct and allowed the different diseases to be distinguished. All lymphoid tumours expressed leucocyte common antigen, with B cell tumours staining with MB1 and MB2, and T cell tumours staining with MT1 and UCHL1. T cell acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma all stained with MT1, but some were negative with UCHL1. B cell ALL/lymphoblastic lymphoma also stained with MT1, but could be distinguished by its reactivity with MB1 and MB2. Reed-Sternberg cells did not stain with any reagent. Normal and neoplastic myeloid cells stained with MT1. Carcinomas stained with CAM 5.2 but were negative for lymphoid markers except MB2 staining in some cases. A case of neuroblastoma could be distinguished from ALL/lymphoblastic lymphoma by its lack of reactivity with all antileucocyte antibodies and its staining with antineurone specific enolase. Although not ideal, if used together, this panel of reagents may usefully be applied to routinely fixed and processed, decalcified bone marrow trephines.

Haematological validation of a computer-based bone marrow reporting system.

AIMS: To prove the safety and effectiveness of "Professor Belmonte", a knowledge-based system for bone marrow reporting, a formal evaluation of the reports generated by the system was performed. METHODS: Three haematologists (a consultant, a senior registrar, and a junior registrar), none of whom were involved in the development of the software, compared the unedited reports generated by Professor Belmonte with the original bone marrow reports in 785 unselected cases. Each haematologist independently graded the quality of Belmonte's reports using one of four categories: (a) better than the original report (more informative, containing useful information missing in the original report); (b) equivalent to the original report; (c) satisfactory, but missing information that should have been included; and (d) unsatisfactory. RESULTS: The consultant graded 64 reports as more informative than the original, 687 as equivalent to the original, 32 as satisfactory, and two as unsatisfactory. The senior registrar considered 29 reports to be better than the original, 739 to be equivalent to the original, 15 to be satisfactory, and two to be unsatisfactory. The junior registrar found that 88 reports were better than the original, 681 were equivalent to the original, 14 were satisfactory, and two were unsatisfactory. Each judge found two different reports to be unsatisfactory according to their criteria. All 785 reports generated by the computer system received at least two scores of satisfactory or better. CONCLUSIONS: In this representative study, Professor Belmonte generated bone marrow reports that proved to be as accurate as the original reports in a large university hospital. The haematology knowledge contained within the system, the reasoning process, and the function of the software are safe and effective for assisting haematologists in generating high quality bone marrow reports.