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Acute promyelocytic leukaemia after treatment for seminoma with carboplatin
3
Ortega YR, Sterling CR, Gilman RH, Cama VA, Diaz F. Cyclospora species: a new protozoan pathogen of humans. N Engl J Med 1993; 328: 1308-12.
4
5
Pollok RCG, Bendall RP, Moody A, Chiodini PL, Churchill DR. Traveller’s diarrhoea associated with cyanobacterium-like bodies. Lancet 1992; 340: 556-57. Centers for Disease Control and Prevention. Outbreaks of diarrheal illness associated with cyanobacteria (blue-green algae)-like bodies: Chicago and Nepal, 1989 and 1990. MMWR 1991; 40: 325-27.
Acute promyelocytic leukaemia after treatment for seminoma with carboplatin SIR-It is increasingly recognised that previous treatment with DNA topoisomerase II inhibitors (including etoposide, cisplatin, anthracyclines, mitozantrone, and razoxane) is associated with therapy-related acute myeloid leukaemia (tAML).’ Carboplatin, a platinum analogue that is potentially less toxic than cisplatin, may also be associated with secondary myelodysplasia and tAML. Colon-Otero et aP reported three cases of secondary myelodysplasia and AML after treatment of ovarian carcinoma with combination chemotherapy containing carboplatin. However, they admit that it was difficult to establish the role of carboplatin because all three patients had received cyclophosphamide, and two had also received cisplatin. We report a case of acute promyelocytic leukaemia after treatment with singleagent carboplatin. A 38-year-old white man presented to our unit with fever due to perianal sepsis. Full blood count showed pancytopenia with haemoglobin concentration 64 g/L, white cell count 0.5x109/L, and platelet count 17X10"/L. Bone marrow aspirate was hypercellular and revealed a predominance of atypical promyelocytes (47% of nucleated cells) containing granules and multiple Auer rods, and myeloid blasts (38% of nucleated cells). The promyelocytes showed 100% positivity with myeloperoxidase. Flow cytometric immunophenotyping showed that the leukaemic cells were positive for CD13 (72-3%) and CD33 (68-2%) with only a few cells expressing CD34 (23-4%) and HLADR (7-1%). Cytogenetic analysis demonstrated t(15:17) confirming the diagnosis of hypergranular acute promyelocytic leukaemia (FAB M3). Coagulation studies showed mild disseminated intravascular coagulation. 6 years previously the patient had been diagnosed with seminoma of the right testis associated with para-aortic lymphadenopathy, and right-sided hydronephrosis and renal impairment. Treatment had consisted of orchidectomy followed by four courses of single-agent carboplatin with a total cumulative dose of 2-9 g calculated according to Calvert et al.3 The following year relapse was detected radiologically and biochemically (from rising beta-human chorionic gonadotropin) and a total dose of 35 Gy of megavoltage radiotherapy was given in daily fractions over four weeks to the para-aortic and pelvic regions. After the radiotherapy he remained in full clinical, radiological, and biochemical remission. He was randomised to the Medical Research Council AML 10 protocol and cytological and cytogenetic remission was achieved with tretinoin 45 mg/m2,
daunorubicin 50 mg/m2
on days 1, 3, 5, etoposide 100 mg/m2 on days 1-5, and cytarabine 100 mg/m2 twice daily on days 1-10. Three courses of combination chemotherapy were given as consolidation and the patient is presently well. Like the report of Colon-Otero and colleagues,2 which suggests that carboplatin may be leukaemogenic, there have been many descriptions of treatment with cisplatin in combination chemotherapy being followed by AML. However, there is only one case report of leukaemia after single-agent cisplatin, in which acute promyelocytic
leukaemia followed treatment for bladder cancer.’ It is interesting that Bhavani et al’ postulate that DNA topoisomerase II inhibitors (which include platinum compounds) are the class of drugs most likely to result in therapy-related acute promyelocytic leukaemia. Although it is not established that local megavoltage radiotherapy given alone is leukaemogenic, the intermediate dose that our patient received approximates to that given to patients receiving extended field inverted-Y treatment for Hodgkin’s disease and, hence, it is conceivable that it may have acted in conjunction with the chemotherapy in a manner similar to the findings of Andrieu et a1.5 Against this, however, is the observation that the cytogenetic abnormalities, which frequently are multiple and involve chromosomes 5 or 7, are not characteristic of radiation-induced leukaemia. J A Snowden, S T Laidlaw, A E
Champion, J
T Reilly
Department of Haematology, Northern General Hospital, Sheffield S5 7AU, UK; Department of Clinical Oncology, Weston Park Hospital, Sheffield
1 2
3
4
5
and
Bhavani M, Al Azzawi S, Liu Yin JA, Lucas GS. Therapy-related promyelocytic leukaemia. Br J Haematol 1994; 86: 231-33. Colon-Otero G, Malkasian GD, Edmonson JH. Secondary myelodysplasia and acute myeloid leukaemia following carboplatin containing combination chemotherapy for ovarian carcinoma. J Natl Cancer Inst 1993; 85: 1858-60. Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989; 7: 1748-56. Bassett WB, Weiss RB. Acute leukaemia following cisplatin for bladder cancer: a case report. J Clin Oncol 1986; 4: 614. Andrieu JM, Ifrah N, Payan C. Increased risk of secondary acute nonlymphocytic leukaemia after extended field radiation therapy combined with MOPP chemotherapy for Hodgkin’s disease. J Clin Oncol 1990; 8: 1148-54.
Human herpesvirus 6 DNA in skin biopsy tissue from marrow graft recipients with severe combined immunodeficiency SIR-Michel and colleagues (Sept 3, p 686) report detection of human herpesvirus 6 (HHV-6) DNA in skin biopsy tissue from an infant with an exanthematous papular rash developing 16 months after bone marrow transplantation (BMT) for severe combined immunodeficiency. They claim that HHV-6 DNA has not previously been detected in exanthematous skin from BMT patients with severe combined immunodeficiency. We are conducting a three-year prospective study of both cytomegalovirus (CMV) and HHV-6 infection in skin and rectal biopsy tissue from a cohort of adult and paediatric BMT recipients, with immunohistochemistry and PCR. 8 of the 57 patients were transplanted for severe combined immunodeficiency and 2 for osteopetrosis, the conditioning for which is the same (cyclophosphamide and busulphan). HHV-6 DNA was detected in skin biopsy tissue by nested PCR in 4 of the 8 patients with combined immunodeficiency and in both patients with osteopetrosis (age 5-9 months). None of the patients simultaneously had CMV DNA in biopsy specimens by PCR. All 6 patients had an exanthematous papular rash at the time of biopsy, and in all 6 cases histological analysis of the skin biopsy sample yielded a positive histopathological diagnosis: both osteopetrosis patients had dermatitis (in common with Michel and coworkers’ patient) and the 4 patients with combined immunodeficiency had graft-versus-host disease (GVHD), ranging in severity from mild (histological grade I) to very severe
(histological grade III).
The role of HHV-6in skin
is unclear; however,
biopsy tissue in these patients preceding or concurrent herpes virus 1361
Ortega YR, Sterling CR, Gilman RH, Cama VA, Diaz F. Cyclospora species: a new protozoan pathogen of humans. N Engl J Med 1993; 328: 1308-12.
4
5
Pollok RCG, Bendall RP, Moody A, Chiodini PL, Churchill DR. Traveller’s diarrhoea associated with cyanobacterium-like bodies. Lancet 1992; 340: 556-57. Centers for Disease Control and Prevention. Outbreaks of diarrheal illness associated with cyanobacteria (blue-green algae)-like bodies: Chicago and Nepal, 1989 and 1990. MMWR 1991; 40: 325-27.
Acute promyelocytic leukaemia after treatment for seminoma with carboplatin SIR-It is increasingly recognised that previous treatment with DNA topoisomerase II inhibitors (including etoposide, cisplatin, anthracyclines, mitozantrone, and razoxane) is associated with therapy-related acute myeloid leukaemia (tAML).’ Carboplatin, a platinum analogue that is potentially less toxic than cisplatin, may also be associated with secondary myelodysplasia and tAML. Colon-Otero et aP reported three cases of secondary myelodysplasia and AML after treatment of ovarian carcinoma with combination chemotherapy containing carboplatin. However, they admit that it was difficult to establish the role of carboplatin because all three patients had received cyclophosphamide, and two had also received cisplatin. We report a case of acute promyelocytic leukaemia after treatment with singleagent carboplatin. A 38-year-old white man presented to our unit with fever due to perianal sepsis. Full blood count showed pancytopenia with haemoglobin concentration 64 g/L, white cell count 0.5x109/L, and platelet count 17X10"/L. Bone marrow aspirate was hypercellular and revealed a predominance of atypical promyelocytes (47% of nucleated cells) containing granules and multiple Auer rods, and myeloid blasts (38% of nucleated cells). The promyelocytes showed 100% positivity with myeloperoxidase. Flow cytometric immunophenotyping showed that the leukaemic cells were positive for CD13 (72-3%) and CD33 (68-2%) with only a few cells expressing CD34 (23-4%) and HLADR (7-1%). Cytogenetic analysis demonstrated t(15:17) confirming the diagnosis of hypergranular acute promyelocytic leukaemia (FAB M3). Coagulation studies showed mild disseminated intravascular coagulation. 6 years previously the patient had been diagnosed with seminoma of the right testis associated with para-aortic lymphadenopathy, and right-sided hydronephrosis and renal impairment. Treatment had consisted of orchidectomy followed by four courses of single-agent carboplatin with a total cumulative dose of 2-9 g calculated according to Calvert et al.3 The following year relapse was detected radiologically and biochemically (from rising beta-human chorionic gonadotropin) and a total dose of 35 Gy of megavoltage radiotherapy was given in daily fractions over four weeks to the para-aortic and pelvic regions. After the radiotherapy he remained in full clinical, radiological, and biochemical remission. He was randomised to the Medical Research Council AML 10 protocol and cytological and cytogenetic remission was achieved with tretinoin 45 mg/m2,
daunorubicin 50 mg/m2
on days 1, 3, 5, etoposide 100 mg/m2 on days 1-5, and cytarabine 100 mg/m2 twice daily on days 1-10. Three courses of combination chemotherapy were given as consolidation and the patient is presently well. Like the report of Colon-Otero and colleagues,2 which suggests that carboplatin may be leukaemogenic, there have been many descriptions of treatment with cisplatin in combination chemotherapy being followed by AML. However, there is only one case report of leukaemia after single-agent cisplatin, in which acute promyelocytic
leukaemia followed treatment for bladder cancer.’ It is interesting that Bhavani et al’ postulate that DNA topoisomerase II inhibitors (which include platinum compounds) are the class of drugs most likely to result in therapy-related acute promyelocytic leukaemia. Although it is not established that local megavoltage radiotherapy given alone is leukaemogenic, the intermediate dose that our patient received approximates to that given to patients receiving extended field inverted-Y treatment for Hodgkin’s disease and, hence, it is conceivable that it may have acted in conjunction with the chemotherapy in a manner similar to the findings of Andrieu et a1.5 Against this, however, is the observation that the cytogenetic abnormalities, which frequently are multiple and involve chromosomes 5 or 7, are not characteristic of radiation-induced leukaemia. J A Snowden, S T Laidlaw, A E
Champion, J
T Reilly
Department of Haematology, Northern General Hospital, Sheffield S5 7AU, UK; Department of Clinical Oncology, Weston Park Hospital, Sheffield
1 2
3
4
5
and
Bhavani M, Al Azzawi S, Liu Yin JA, Lucas GS. Therapy-related promyelocytic leukaemia. Br J Haematol 1994; 86: 231-33. Colon-Otero G, Malkasian GD, Edmonson JH. Secondary myelodysplasia and acute myeloid leukaemia following carboplatin containing combination chemotherapy for ovarian carcinoma. J Natl Cancer Inst 1993; 85: 1858-60. Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989; 7: 1748-56. Bassett WB, Weiss RB. Acute leukaemia following cisplatin for bladder cancer: a case report. J Clin Oncol 1986; 4: 614. Andrieu JM, Ifrah N, Payan C. Increased risk of secondary acute nonlymphocytic leukaemia after extended field radiation therapy combined with MOPP chemotherapy for Hodgkin’s disease. J Clin Oncol 1990; 8: 1148-54.
Human herpesvirus 6 DNA in skin biopsy tissue from marrow graft recipients with severe combined immunodeficiency SIR-Michel and colleagues (Sept 3, p 686) report detection of human herpesvirus 6 (HHV-6) DNA in skin biopsy tissue from an infant with an exanthematous papular rash developing 16 months after bone marrow transplantation (BMT) for severe combined immunodeficiency. They claim that HHV-6 DNA has not previously been detected in exanthematous skin from BMT patients with severe combined immunodeficiency. We are conducting a three-year prospective study of both cytomegalovirus (CMV) and HHV-6 infection in skin and rectal biopsy tissue from a cohort of adult and paediatric BMT recipients, with immunohistochemistry and PCR. 8 of the 57 patients were transplanted for severe combined immunodeficiency and 2 for osteopetrosis, the conditioning for which is the same (cyclophosphamide and busulphan). HHV-6 DNA was detected in skin biopsy tissue by nested PCR in 4 of the 8 patients with combined immunodeficiency and in both patients with osteopetrosis (age 5-9 months). None of the patients simultaneously had CMV DNA in biopsy specimens by PCR. All 6 patients had an exanthematous papular rash at the time of biopsy, and in all 6 cases histological analysis of the skin biopsy sample yielded a positive histopathological diagnosis: both osteopetrosis patients had dermatitis (in common with Michel and coworkers’ patient) and the 4 patients with combined immunodeficiency had graft-versus-host disease (GVHD), ranging in severity from mild (histological grade I) to very severe
(histological grade III).
The role of HHV-6in skin
is unclear; however,
biopsy tissue in these patients preceding or concurrent herpes virus 1361