- Email: [email protected]
MITOZANTRONE AND HIGH-DOSE CYTARABINE IN ADULT ACUTE MYELOID LEUKAEMIA
1384 of chemotherapy with this combination after peripheral blood recovery. Both patients had prolonged thrombocytopenia resolving after eight weeks. No patient has had symptomatic cardiotoxicity. The combination of cytarabine and MTZ is both effective and well tolerated even in heavily pretreated patients and deserves wider trial both in relapsed patients and as part of the intensive consolidation therapy of AML. course
Letters
to
the Editor
MITOZANTRONE AND HIGH-DOSE CYTARABINE IN ADULT ACUTE MYELOID LEUKAEMIA
SIR,-The management of relapsed acute myeloid leukaemia (AML) is complicated both by the resistance to chemotherapy of the relapsed clone, and by the cumulative cardiotoxicity of anthracyclines used during initial induction and consolidation chemotherapy. We report our initial experience with the anthracenedione derivative mitozantrone (MTZ), which is effective in inducing new complete remissions and is relatively noncardiotoxic in patients with relapsed AML.1 We have treated eighteen patients with this agent in combination with high-dose cytarabine (Ara-C), which is also effective remission induction therapy in a percentage of heavily pretreated patients.2 TABLE I-CYTARABINE/MTZ IN PATIENTS WITH AML
MRC Leukaemia
Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W120HS
Department of Haematology,
R. E. MARCUS D. CATOVSKY J. M. GOLDMAN D. A. G. GALTON A. C. NEWLAND
London Hospital, E 1
G. SLOCOMBE
Department of Haematology, Ealing Hospital
U. HEGDE
Robbins G, Ma DDF, Ho A. Sequential studies on the role of the treatment of acute leukemia. Cancer Treatment Rep 1983; 10 (suppl B): 57-63. 2. Rudnick YM, Cadman EC, Capizzi RL, Skeel JM, Bertino JR, Mclntosh HD High dose Ara-C in refractory acute leukemia. Cancer 1979; 44: 1189-93. 3 Marcus RE, Catovsky D, Goldman JM, Worsley AM, Galton DAG Maintenance and consolidation chemotherapy in AML. Lancet 1984; i. 686-87 1. Prentice
HG,
mitoxantrone in
!
I
MEDICAL MANAGEMENT OF PYOGENIC LIVER ABSCESSES
16 patients with relapsed AML (13 in first relapse and 3 in second) primary refractory AML were treated with MTZ 12 infusion daily for five days and with mg/m2 rapid 2 h infusion twice daily for 3 days (table r). 10 1 g/m by cytarabine patients achieved complete remission (CR), 6 after one course; 3 had a partial response; and 5 did not respond and died of infection or leukaemia within two weeks. Of the 10 patients entering CR 8 had previously relapsed after completion of consolidation chemotherapy for primary or relapsed AML. In contrast, only 1 patient out of 6 who relapsed while still receiving consolidation chemotherapy achieved CR. 1 of the 2 patients with AML refractory to our standard AML induction treatment3entered CR after three courses of cytarabine/MTZ and remains alive and well four months after entering CR. Of the 10 remitters, 2 have had an allogeneic bone marrow transplant in second CR and are alive and well eight and twenty weeks later. 4 patients relapsed again within two months. 4 patients remain in CR between twelve and twentyeight weeks after completing treatment, having received either one or two consolidation courses with these same agents after peripheral blood recovery. The chemotherapy was generally well tolerated, nausea being the most serious side effect. The duration of neutropenia and thrombocytopenia varied from ten to twenty-two days. All patients had previously received anthracyclines. Six had had more than 450 and 4 more than 600 mg/m2. Cardiac toxicity consisting of exertional dyspnoea was seen in two patients who had previously received more than 600 mg/m2of anthracycline. It responded partly to digoxin and diuretics. Encouraged by these results in relapsed patients we have also used this combination to treat four new patients with AML. We have reduced the dosages according to the age of the patient. All achieved CR after one course (table 11). 2 patients have received a second
and 2 with
by
intravenous
mg/m2
TABLE 11-NEW PATIENTS TREATED WITH CYTARABINE/MTZ I
I
I
SIR,-Dr McCorkell and Dr Niles’ report (April 6, p 803) on the failure of medical therapy in 13 of 14 patients with pyogenic liver abscesses contrasts with the success that we and others have reported.’ Their poor results may be partly due to factors such as the long duration of symptoms before treatment and the presence of underlying diseases (including echinococcal cysts and hepatoma), tuberculosis, or aspergillosis in some patients. However, the most important factor seems to be the lack of attention to anaerobic pathogens. No anaerobes were analysed, indicating that appropriate culture techniques may not have been used. Similarly, the medical therapy utilised in most of their patients lacked activity against common enteric anaerobes (especially Bacteroidesfragilis). We and others have emphasised the role of anaerobes in pyogenic liver abscesses: "Non-spore-forming anaerobic bacteria are recognised as the most numerous and important pathogens in pyogenic liver abscess. These infections are usually polymicrobial".2The empirical therapy of these infections requires antimicrobial agents that are active against the expected enteric pathogens, both aerobic and anaerobic; we commonly use gentamicin and clindamycin, although cefoxitin, chloramphenicol, the carboxy and acyclaminopenicillins, third generation cephalosporins, and metronidazole may also be appropriate in various combinations. Broad-spectrum antibiotic therapy should be narrowed only when it is certain that all significant pathogens have been identified on the basis of appropriate cultures, including techniques that reliably identify anaerobes. Where this information is not available, broad-spectrum therapy should be continued for the entire course. With this approach we have had consistent success with non-surgical therapy for patients with pyogenic liver abscesses. Division of Infectious Diseases, Kaiser Permanente Medical Center, Bellflower, California 90706, USA; and Los Angeles
DAVID A. HERBERT
Division of Gastroenterology, San Pedro Peninsula Hospital
DAVID A. FOGEL
Division of Hepatology, Kaiser Permanente Medical Center, Los Angeles
FRED SIMMONS
Division of Infectious Diseases, Kaiser Permanente Medical Centre, Los Angeles
JOEL RUSKIN
1. Herbert DA, Fogel DA, Rothman J, Wilson S, Simmons F, Ruskin J Pyogenic liver abscesses: successful non-surgical therapy. Lancet 1982, i 134-36. 2 Sabbaj J. Anaerobes in liver abscess. Rev Inf Dis 1984; 6: S152-S156.
Letters
to
the Editor
MITOZANTRONE AND HIGH-DOSE CYTARABINE IN ADULT ACUTE MYELOID LEUKAEMIA
SIR,-The management of relapsed acute myeloid leukaemia (AML) is complicated both by the resistance to chemotherapy of the relapsed clone, and by the cumulative cardiotoxicity of anthracyclines used during initial induction and consolidation chemotherapy. We report our initial experience with the anthracenedione derivative mitozantrone (MTZ), which is effective in inducing new complete remissions and is relatively noncardiotoxic in patients with relapsed AML.1 We have treated eighteen patients with this agent in combination with high-dose cytarabine (Ara-C), which is also effective remission induction therapy in a percentage of heavily pretreated patients.2 TABLE I-CYTARABINE/MTZ IN PATIENTS WITH AML
MRC Leukaemia
Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W120HS
Department of Haematology,
R. E. MARCUS D. CATOVSKY J. M. GOLDMAN D. A. G. GALTON A. C. NEWLAND
London Hospital, E 1
G. SLOCOMBE
Department of Haematology, Ealing Hospital
U. HEGDE
Robbins G, Ma DDF, Ho A. Sequential studies on the role of the treatment of acute leukemia. Cancer Treatment Rep 1983; 10 (suppl B): 57-63. 2. Rudnick YM, Cadman EC, Capizzi RL, Skeel JM, Bertino JR, Mclntosh HD High dose Ara-C in refractory acute leukemia. Cancer 1979; 44: 1189-93. 3 Marcus RE, Catovsky D, Goldman JM, Worsley AM, Galton DAG Maintenance and consolidation chemotherapy in AML. Lancet 1984; i. 686-87 1. Prentice
HG,
mitoxantrone in
!
I
MEDICAL MANAGEMENT OF PYOGENIC LIVER ABSCESSES
16 patients with relapsed AML (13 in first relapse and 3 in second) primary refractory AML were treated with MTZ 12 infusion daily for five days and with mg/m2 rapid 2 h infusion twice daily for 3 days (table r). 10 1 g/m by cytarabine patients achieved complete remission (CR), 6 after one course; 3 had a partial response; and 5 did not respond and died of infection or leukaemia within two weeks. Of the 10 patients entering CR 8 had previously relapsed after completion of consolidation chemotherapy for primary or relapsed AML. In contrast, only 1 patient out of 6 who relapsed while still receiving consolidation chemotherapy achieved CR. 1 of the 2 patients with AML refractory to our standard AML induction treatment3entered CR after three courses of cytarabine/MTZ and remains alive and well four months after entering CR. Of the 10 remitters, 2 have had an allogeneic bone marrow transplant in second CR and are alive and well eight and twenty weeks later. 4 patients relapsed again within two months. 4 patients remain in CR between twelve and twentyeight weeks after completing treatment, having received either one or two consolidation courses with these same agents after peripheral blood recovery. The chemotherapy was generally well tolerated, nausea being the most serious side effect. The duration of neutropenia and thrombocytopenia varied from ten to twenty-two days. All patients had previously received anthracyclines. Six had had more than 450 and 4 more than 600 mg/m2. Cardiac toxicity consisting of exertional dyspnoea was seen in two patients who had previously received more than 600 mg/m2of anthracycline. It responded partly to digoxin and diuretics. Encouraged by these results in relapsed patients we have also used this combination to treat four new patients with AML. We have reduced the dosages according to the age of the patient. All achieved CR after one course (table 11). 2 patients have received a second
and 2 with
by
intravenous
mg/m2
TABLE 11-NEW PATIENTS TREATED WITH CYTARABINE/MTZ I
I
I
SIR,-Dr McCorkell and Dr Niles’ report (April 6, p 803) on the failure of medical therapy in 13 of 14 patients with pyogenic liver abscesses contrasts with the success that we and others have reported.’ Their poor results may be partly due to factors such as the long duration of symptoms before treatment and the presence of underlying diseases (including echinococcal cysts and hepatoma), tuberculosis, or aspergillosis in some patients. However, the most important factor seems to be the lack of attention to anaerobic pathogens. No anaerobes were analysed, indicating that appropriate culture techniques may not have been used. Similarly, the medical therapy utilised in most of their patients lacked activity against common enteric anaerobes (especially Bacteroidesfragilis). We and others have emphasised the role of anaerobes in pyogenic liver abscesses: "Non-spore-forming anaerobic bacteria are recognised as the most numerous and important pathogens in pyogenic liver abscess. These infections are usually polymicrobial".2The empirical therapy of these infections requires antimicrobial agents that are active against the expected enteric pathogens, both aerobic and anaerobic; we commonly use gentamicin and clindamycin, although cefoxitin, chloramphenicol, the carboxy and acyclaminopenicillins, third generation cephalosporins, and metronidazole may also be appropriate in various combinations. Broad-spectrum antibiotic therapy should be narrowed only when it is certain that all significant pathogens have been identified on the basis of appropriate cultures, including techniques that reliably identify anaerobes. Where this information is not available, broad-spectrum therapy should be continued for the entire course. With this approach we have had consistent success with non-surgical therapy for patients with pyogenic liver abscesses. Division of Infectious Diseases, Kaiser Permanente Medical Center, Bellflower, California 90706, USA; and Los Angeles
DAVID A. HERBERT
Division of Gastroenterology, San Pedro Peninsula Hospital
DAVID A. FOGEL
Division of Hepatology, Kaiser Permanente Medical Center, Los Angeles
FRED SIMMONS
Division of Infectious Diseases, Kaiser Permanente Medical Centre, Los Angeles
JOEL RUSKIN
1. Herbert DA, Fogel DA, Rothman J, Wilson S, Simmons F, Ruskin J Pyogenic liver abscesses: successful non-surgical therapy. Lancet 1982, i 134-36. 2 Sabbaj J. Anaerobes in liver abscess. Rev Inf Dis 1984; 6: S152-S156.