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.

Myelodysplastic syndrome associated with trisomy 2.

Clinical course and cytogenetic analysis suggest that myelodysplasia (MDS) is one step in a multistep model of malignant transformation of haematopoietic stem cells to acute myeloid leukaemia (AML). We report a further case of MDS associated with trisomy 2, and comment on the significance of the cytogenetic abnormality, which as a sole abnormality only occurs in MDS, but is found in combination with other chromosomal abnormalities in AML. Previous reports on balanced and unbalanced chromosomal abnormalities associated with therapy related MDS and therapy related AML suggest that trisomy 2 is an early chromosomal abnormality in leukaemogenesis.

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.

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.

Genetic susceptibility to Hodgkin's disease and secondary neoplasias: FISH analysis reveals patients at high risk of developing secondary neoplasia.

BACKGROUND: Cytotoxic drugs administered before high-dose therapy (HDT) represent a significant factor in the development of leukemic complications in patients with lymphoid malignancies. This retrospective study was used to detect evidence of abnormal therapy-related myelodysplasia/secondary acute myeloid leukaemia (tMDS/sAML) clones before HDT in a subset of patients who subsequently developed secondary neoplasia. PATIENTS AND METHODS: 230 patients with non-Hodgkin's lymphoma (NHL) underwent HDT comprising cyclophosphamide and total body irradiation (TBI) with autologous hematopoietic progenitor-cell support. Thirty-three patients have developed tMDS/sAML and 20 of these were screened for the presence of emerging therapy-related abnormalities before HDT. A further 24 patients without evidence of secondary neoplasia were screened using fluorescence in situ hybridisation (FISH). RESULTS: Significant levels of abnormal cells were identified in 20/20 patients screened who have developed secondary neoplasia compared with only three of 24 patients in the HDT control group who have not. The latter three patients have since died. CONCLUSIONS: The triple FISH assay was developed to detect loss of chromosomal material from 5q31, 7q22 and 13q14. It can potentially identify those patients at risk of alkylating agent-induced leukaemia before they proceed to HDT. Used in a prospective manner, the triple FISH assay could permit more informed clinical management.

Loss of CD20 expression following treatment with rituximab (chimaeric monoclonal anti-CD20): a retrospective cohort analysis.

A retrospective analysis of CD20 expression following rituximab for B-cell non-Hodgkin's lymphoma demonstrated a significant change in immunophenotype in 6/25 (24%) patients with persistent bone marrow (BM) infiltration. In three out of six patients, the B cells were uniformly CD20-/CD79alpha+, consistent with frank loss of CD20 expression. In the remaining three cases, the BM infiltrate was predominantly (> 80%) CD20-/CD79alpha+. Two of the former but none of the latter three cases achieved a clinical response. In three further cases, the post-treatment BM infiltrate was composed entirely of benign or reactive CD3+ T cells. Frank loss of CD20 was not seen in 25 post-treatment lymph node biopsies. Immunophenotyping is therefore an important adjunct in the diagnosis of BM infiltration following rituximab.

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.

Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia.

Between 1972 and 1988, 832 consecutive patients were treated for acute leukaemia at St. Bartholomew's Hospital; a retrospective analysis has been conducted to determine the clinical course and outcome for 101 who have survived > or = 10 years following treatment. At a median follow-up of 16 years (range 10-28 years), 86 patients (86 out of 834 total, 11%) were still alive. Long-term follow-up of patients who have survived > or = 10 years following treatment for acute leukaemia revealed that most patients were in normal health, although a significant number of complications had occurred.

Acute Myelogenous Leukaemia in Patients 60 Years and Older: A Retrospective Analysis from St Bartholomew's Hospital 1969-1999.

Between 1969 and 1999, 420 patients (age > 60 years) with newly diagnosed AML were managed at St Bartholomew's Hospital (SBH), London, UK. Sixty-nine percent of patients received therapy with curative intent Eighty-eight patients (31%) of the latter achieved complete remission (CR), representing an overall CR rate of 21%. Treatment failure due to early death (ED) and resistant disease (RD) occurred in 50 and 19%, respectively. With median follow up of 11 years, actuarial survivals at 1,3 and 5 years were 20, 7 and 4%, respectively, the median survival of the entire cohort was 2 months. For patients who achieved CR, median survival was significantly better than that of patients in whom treatment failed (14 vs. 6 months). Over the 30 years, CR rate and the relative incidence of RD both increased from 13 to 45%, and 3 to 27%, respectively, whilst ED rate reduced from 84 to 27%. Multivariate analysis showed that treatment era, hepatosplenomegaly and increasing age predicted for reduced CR rate and OS. Although elderly patients with AML are characterised by a poor response to intensive chemotherapy, significant improvements in supportive care and the delivery of intensive treatment have led to improved CR rates and OS. New therapeutic strategies and a greater awareness of prognostic factors may further improve clinical outcome in this important group of patients.

High-dose treatment with autologous bone marrow support as consolidation of first remission in younger patients with acute myelogenous leukaemia.

BACKGROUND: Debate and controversy remain as to the optimal post-remission therapy for younger patients with acute myelogenous leukaemia (AML). The aim of this study was to evaluate high-dose treatment (HDT) with autologous bone marrow support (ABMS) as consolidation of first complete remission (CR). PATIENTS AND METHODS: One hundred forty-four patients (AML-M3 excluded, median age 38 years, range 15-49 years) received remission induction therapy comprising: adriamycin 25 mg/m2, days 1-3, cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m2 bid, days 1-7. Patients in whom CR was achieved received two further cycles of the same treatment prior to bone marrow being harvested and cryopreserved. HDT comprised ara-C: 1 g/m2 b.i.d. x six days and total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawed autologous marrow was then re-infused. RESULTS: Complete remission was achieved in 106 of 144 patients (73%) who were thus eligible to receive ara-C + TBI + ABMS; 61 actually received it. Following HDT, the median time to neutrophil recovery (> 0.5 x 10(9)/l) was 25 days (range 11-72 days) and to platelet recovery (> 20 x 10(9)/l), 42 days (range 15-159 days). There were eight treatment-related deaths. Analysis by 'intention to treat' shows both remission duration (log-rank, P = 0.001) and survival (log-rank, P = 0.004) to be significantly longer for the 106 patients eligible to receive HDT than for a historical control group (n = 133) who received identical remission induction and consolidation therapy but without ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106 patients remain in CR (37%) and 54 (51% of those in whom CR was achieved) remain alive, with a predicted actuarial survival of 52% at 5 years. CONCLUSIONS: The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.

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.

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.

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.

IDEC-C2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin's lymphoma and lymphoproliferative disorders: evaluation of response on 48 patients.

This study focused on the efficacy of IDEC-C2B8 (chimeric anti-CD20) immunotherapy relative to specific subtypes of low-grade lymphoproliferative disorders/non-Hodgkin's lymphomas (LPD/NHL). Forty-eight patients with resistant or relapsed disease completed the IDEC-C2B8 infusion schedule of 375 mg/m2/wk x 4 wk. The LPD/NHL subtypes included: (a) follicular centre cell lymphoma (FCC) in 22 patients; (b) mantle cell lymphoma (MCL) in 10; (c) 1 diffuse large cell lymphoma (DLCL); and (d) the category of small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL) and related disorders in 15 patients. No patient obtained a complete remission. Ten patients (21%) achieved partial remission: 6 FCC, 2 MCL, 1 DLCL and 1 patient from the SLL/CLL group. Twenty-eight patients had stable disease and 10 progressed during immunotherapy. In patients with CLL and MCL in leukaemic phase, there was no correlation between the marked decrease in circulating neoplastic cells following antibody infusions and amelioration of the tumour burden. The results suggest that the subtype of LPD/NHL and the intensity of CD20 on the tumour cells influence the effectiveness of IDEC-C2B8. The antibody was most efficacious against FCC lymphoma. The efficacy (at the dose schedule of 375 mg/m2/wk x 4) against MCL and SLL/CLL appeared to be limited, however.

High-dose therapy with autologous haematopoietic support in patients with transformed follicular lymphoma: a study of 27 patients from a single centre.

BACKGROUND: The prognosis of patients with transformed follicular lymphoma (FL-t) is poor. The use of high-dose therapy (HDT) with autologous haematopoietic support was therefore evaluated as consolidation of remission. PATIENTS AND METHODS: Twenty-seven patients received high-dose cyclophosphamide and total body irradiation (cyclo + TBI) with autologous bone marrow (BM; n = 24) or peripheral blood progenitor cell support (PBPC; n = 3). BM was treated in vitro with anti-B cell antibodies and complement. Nineteen of 27 patients were treated in first stable remission following transformation. Eight other patients with a history of transformation were treated following a subsequent recurrence of follicular lymphoma (FL). RESULTS: With a median follow-up of 2.4 years, 14 of 27 patients remain alive and in remission; five are alive and free of disease at more than four years. The median survival is 8.5 years. There were two 'early' treatment-related deaths of respiratory failure, and two 'late' deaths of myelodysplastic syndrome (MDS) in remission of lymphoma at 2.8 and 8.5 years. Seven of nine patients having had a recurrence underwent re-biopsy. In two, histology revealed FL, in five, transformed follicular lymphoma. One of the patients with recurrent FL is alive without further therapy, and two of five patients with recurrent FL-t are alive and in remission after further chemotherapy. CONCLUSIONS: It is appropriate to consider HDT for younger patients with FL-t in remission. Repeat biopsy should be considered for patients with recurrent disease. There is a risk of late MDS in patients undergoing this treatment.

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.

Thrombo-embolic disease after splenectomy for hereditary stomatocytosis.

Nine cases of hereditary stomatocytosis (HSt) are presented which show documented thrombotic complications after splenectomy. In three cases, patients became severely ill with pulmonary hypertension and a fourth developed portal hypertension. One unsplenectomized affected adult relative had suspected but unconfirmed thrombotic pathology; the six other affected unsplenectomized adults did not. Since splenectomy is of only limited therapeutic benefit in stomatocytosis, it should not be performed without careful consideration. A tendency to iron overload, even without hypertransfusion and irrespective of splenectomy, is evident in many of these patients.

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients.

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1-37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.

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.

Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support in patients with haematological malignancy.

BACKGROUND: Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support is increasingly being used in patients with haematological malignancy considered to be at high risk for recurrence. The results of this approach, in comparison with the previous experience at St. Bartholomew's Hospital (SBH) using autologous bone marrow transplantation form the basis of this report. PATIENTS AND METHODS: 42 patients (age range 18-63 years, median 42 years), deemed to have a poor prognosis with conventional therapy received myelo-ablative therapy with PBPC support. Diagnoses comprised: non-Hodgkin's lymphoma (NHL): 16 patients, Hodgkin's disease (HD): 9, Multiple Myeloma (MM): 12, and solid tumours (ST): 5. PBPC were mobilised using adriamycin: 35 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 orally, days 1-5, followed by G-CSF: 5 micrograms/kg, subcutaneously, for a median of 7 days (range 6-9 days). RESULTS: A total of 67 PBPC collections were performed, 1 being 'sufficient' (i.e. mononuclear cells > or = 1.5 x 10(8)/kg and CD34+ cells > or = 1 x 10(6)/kg) in 21 of the 42 patients. The median time to haematological recovery following reinfusion of PBPC was 13 days for both neutrophils > 0.5 x 10(9)/l and platelets > 20 x 10(9)/l (ranges: 8-27, and 8-48 days, respectively) which is significantly shorter than for patients in the historical control group. Supportive care requirements were also significantly reduced, as was the duration of hospital stay i.e., median 19 days (range 12-73 days) compared with 29 days (range 9-180 days). CONCLUSION: These results confirm rapid blood count recovery following myelo-ablative therapy with PBPC support and the feasibility of this approach.