Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature.

Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had AML M4Eo and, following treatment with adriamycin, cytosine arabinoside, and 6-thioguanine, all achieved complete remission (CR). Neither patient with del(16)(q22) had typical M4Eo morphology at diagnosis; CR was achieved in one and one had resistant leukaemia. Patients with other abnormalities of 16q had blasts of diverse morphology and, although morphologically abnormal eosinophils were seen in three patients, this was not as marked as in the patients with inv(16). CR was achieved in two of the four patients with other abnormalities of 16q but duration of remission was short in both cases. These results suggest that most patients with del(16)(q22) and other abnormalities of 16q22 do not have typical AML M4Eo. Such patients tend to have a worse prognosis, and are more likely to have complex karyotypes typical of secondary leukaemia.     

Myeloma during a decade: Clinical experience in a single centre

One hundred and fifty-six patients with multiple myeloma weretreated over a period of 12 years at St. Bartholomew's Hospital.The progress of the disease was affected in 96/156 patients(61%). Response was defined as achieving a plateau of M component.A partial or complete response was seen in 68/120 patients treatedconventionally (56.5%), and in 28/36 patients treated with high-dosetherapy (77.7%). The median survival of the group as a wholewas 20 months, with a 2-year survival of just over 40%. In the36 patients treated with high-dose therapy, median survivalwas 6 years, and in a small group who have had maintenance Interferontherapy, the median has not yet been reached. In a univariateanalysis, age, intensity of therapy, haemoglobin and creatininelevels were significant, but multivariate analysis showed thatonly age and intensity of therapy were independent predictorsfor survival. The outlook for relapsed patients who showed progressionof disease remains poor, but palliation was best achieved bysteroid and Interferon in combination. Patients who achievecomplete responses and are maintained on Interferon appear tobe doing better both in terms of freedom from symptoms and insurvival, and methods to enable an elderly population to toleratethis form of therapy need to be explored. intensive chemotherapy, maintenance and relapse therapy, myeloma, survival     

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 optimalpost-remission therapy for younger patients with acute myelogenous leukaemia(AML). The aim of this study was to evaluate high-dose treatment (HDT) withautologous bone marrow support (ABMS) as consolidation of first completeremission (CR). Patients and methods:One hundred forty-four patients (AML-M3excluded, median age 38 years, range 15–49 years) received remissioninduction therapy comprising: adriamycin 25 mg/m², days 1–3,cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m²bid, days 1–7. Patients in whom CR was achieved received two furthercycles of the same treatment prior to bone marrow being harvested andcryopreserved. HDT comprised ara-C: 1 g/m² b.i.d. × six daysand total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawedautologous 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 actuallyreceived it. Following HDT, the median time to neutrophil recovery (>0.5× 10⁹/l) was 25 days (range 11–72 days) and to plateletrecovery (>20 × 10⁹/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 patientseligible to receive HDT than for a historical control group (n= 133)who received identical remission induction and consolidation therapy butwithout ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106patients remain in CR (37%) and 54 (51% of those in whom CR wasachieved) remain alive, with a predicted actuarial survival of 52% at5 years. Conclusions:The addition of ara-C + TBI + ABMS to conventionalconsolidation therapy significantly improved remission duration and survivalover those of a historical control group of patients with AML (aged <50,AML-M3 excluded). HDT was, however, associated with significanttreatment-related mortality and slow blood count recovery. The use of ara-C+ TBI supported by peripheral blood progenitor cells should make the treatmentsafer 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.     

Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia

Fourteen patients with poor-risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out-patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.     

Patterns of survival in patients with Hodgkin's disease: Long follow up in a single centre

BACKGROUND:: Prolonged remission can now be induced in the majority of patientswith Hodgkin's disease with chemotherapy and/or irradiation.However, there is a significant proportion of patients in whomthis approach fails, either at presentation or subsequently.Survival is the definitive endpoint to assess treatment efficacy.In this study, the survival patterns of a large group of consecutivepatients treated in a single institution are presented. RESULTS:: The overall median survival was 18.3 years. Clinical remission(complete remission plus good partial remission) was inducedin 443 (85%); the median survival of patients in remission hasnot been reached. Fifty-eight patients achieved responses lessthan clinical remission with initial therapy (partial response)or had progressive disease, the median survival of this groupbeing 1.4 years. With further therapy, remission was subsequentlyinduced in 10; 5 are still alive, 5 have died between 1.9 yearsand 14.3 years. Twenty patients died before completion of therapy.Recurrence has been documented in 147 of the patients in remission(following initial therapy) over a median follow up period of13 years (minimum 5 years). One hundred forty-three of thesepatients were retreated following recurrence (105 chemotherapy,28 radiotherapy, 6 combined modality treatment and 4 surgery).Second remission was induced in 109/143 (76%). There was a trendtowards better second remission induction in patients whosefirst remission was longer than 1 year (p = 0.06). The medianduration of second remission was inferior to first remissionduration (p < 0.001). There was no correlation between durationof first remission and survival following recurrence (p = 0.8)or with duration of second remission (p = 0.54). There was nosignificant difference in duration of second remission betweenpatients who were initially treated with radiotherapy or chemotherapy(p = 0.3). The median survival following second remission was12.0 years, being the same for patients with initially localizeddisease (stages I and II) treated with radiation alone and forpatients with advanced Hodgkin's disease (stages III and IV)treated with chemotherapy. Survival after recurrence is significantlybetter for patients under 50 years at the time of recurrence(p < 0.001). Second recurrence was documented in 46 patients,third remission being reinduced in 22, the median survival ofthe latter being 5.1 years. CONCLUSION:: These results illustrate the importance of prolonged followup in defining the clinical course of patients with HD and arevital for planning experimental chemotherapy at the time oftreatment failure or recurrence. Hodgkin's disease, salvage therapy, recurrence, relapse, resistant disease, chemotherapy, radiotherapy, survival, remission