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Acute myelogenous leukaemia followed by non-Hodgkin's lymphoma in a patient with AIDS
Journal of Infection (1995) 31, 6 9 - 7 0
CASE REPORT
Acute Myelogenous Leukaemia followed by Non-Hodgkin's Lymphoma in a Patient with AIDS Christian Rabaud 1, Vdronique Dorvaux 2, Thierry May 1, Jean Francois Paitel 2, Brigitte Witz 2, Pierre Lederlin 2 and Philippe Canton 1 Departments of 1Infectious and Tropical Diseases and 2Internal Medicine and Haematology, CHU Nancy, France Accepted for publication 24 November 1994
Introduction B cell non-Hodgkin's lymphoma (NHL) is a well known complication of those infected with HIV. Acute myelogenous leukaemia (AML) associated with HIV infection, however, seems to be extremely rare. To our knowledge, we report the first patient with AIDS who developed these malignancies during the same year.
Case Report In 1987, HIV infection was diagnosed in a 30-year-old homosexual man. In February 1992 he presented with cytomegalovirus (CMV) retinitis and was treated with ganciclovir at an initial dose of lOmg/kg/day for 3 weeks, followed by 5 mg/kg/day for 3 months, zidovudine 600mg/day and cotrimoxazole 480mg/day. In April 1993, the patient was readmitted to the hospital with weight loss and progressive weakness. Physical examination only revealed paleness and cachexia. CD4 + lymphocyte count was below 50 x 106/1. Laboratory findings show pancytopenia (haemoglobin (Hb) 4 g/dl; WBC count 9.4: x 109/1 with 40% blood myeloblasts; platelets 10 x 109/1). Bone marrow films revealed 60% myeloblasts (M2, French-American-British cooperative group classification (FAB)). Blast cell histochemical and surface marker findings were typical of myeloblastic leukaemia: positive for peroxidase, CD33 99%, CD15 98%, CD14 97%. Cytogenetic analysis was inconclusive (no mitoses). Epstein Barr virus serology was positive and was not in favour of a recent infection (VCA IgG: +; VCA IgM: - ; EBNA IgG:+). Following induction therapy with
Address correspondence to: Dr Christian Rabaud, Service de Maladies Infectieuses et Tropicales, CHU de Nancy - H6pitaux de Brabois, F - 5 4 5 1 1 Vandoeuvre Cedex, France.
0163~t453/95/040069 +02 $ 0 8 . 0 0 / 0
cytarabine 200 mg/m 2 from day 1 to day 7 and idarubicin 8 mg/m 2 from day 1 to day 5 (May 14), complete remission (CR) was achieved. On July 12 he received consolidation therapy of cytarabine 3 g/m 2 twice daily from day 1 to day 4 and idarubicin lOmg/m 2 from day 5 to day 6. After partial recovery of drug-induced cytopenia (Hb 10 g/dl; WBC 3.2 x 109/1; platelets 63 x 109/1), he developed fever. Chest X-ray showed nodular lesions in the base of both lungs. Broncho-alveolar lavage and biopsy were negative except for CMV. As the lung lesions continued to progress (Figure 1), thoracotomy was performed which revealed a stage IV non-Hodgkins lymphoma (G, Working Formulation1). After two courses of chemotherapy (October 10 and November 12; cyclophosphamide: 750 mg/m 2 day 1; half dose of adriamycin: 2 5 m g / m 2 day 1; vincristine 1.4mg/m 2 day 1; prednisolone 40 mg/m 2from day 1 to day 5) with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), the nodular lesions decreased in size. At the same time, CMV retinitis reappeared and because of persistent cytopenia was treated with foscarnet. (Hb 6g/dl; WBC 0.9 x 109/1; platelets 25 x 109/1). Bone marrow films revealed no myeloblasts. On December 12, the patient died suddenly from air embolism due to an accidental leak of air into the central venous catheter. Post mortem examination revealed decrease in lung NHL lesions: only a single i cm lesion remained and histopathological examination confirmed the presence of lymphoma cells.
Discussion Non-Hodgkins lymphoma occurs frequently in patients with AIDS.2 Only 14 cases of AML in such patients have previously been reported. 3-13 Most frequent were M4 (FAB) (five patients) 4'7'9'1° followed by M2 (FAB) (four © 1995 The British Society for the Study of Infection
70
Acute Myelogenous Leukaemia and that m u c h of the evolution of the NHL occurred after the initiation of this AML therapy. Despite resistance of NHL to cytarabine and idarubicin, cyclophosphamide efficacy remained. The CHOP regimen seems to remain effective for managing NHL in these patients. Much data confirms that malignancies occur more frequently in patients with AIDS t h a n in the general population. 1~ There is no recorded data about secondary malignancies in such patients probably due to their short survival time.
Acknowledgements The authors t h a n k Dr W Canada for his contribution to the manuscript.
References
Figure 1. Non-Hodgkin's l y m p h o m a nodular lesions in both lungs. Chest X-rays: September 22 nd 1993.
patients). 3'6'8'12At least five patients s-7'1°'12 received aggressive induction chemotherapy, three were treated with the protocol cytosine arabinoside for 7 days with daunorubicin for 3 d a y s Y '1° These five patients were all in complete remission with survival rates ranging from 8 - 2 2 + months. In spite of AIDS, our patient tolerated chemotherapy well and about 7 months remission was achieved before his death. As previously reported, s-7'1° we concluded that aggressive chemotherapy was relatively well tolerated in those who were HIV seropositive and patients with AIDS who developed AML, and that complete recession of AML could be achieved. To our knowledge, this is the first case of non-Hodgkins l y m p h o m a diagnosed after AML in a patient with AIDS. The interval between the two diagnoses was 4 months. The delay between AML treatment and the onset of NHL, however, did not suggest a secondary drug-induced NHL. Because this patient's NHL presented within a few months of AML chemotherapy, we think it was already developing when AML therapy was started. Efficacy of the AML therapy used for this patient had previously been proved against high grade NHL. 14 We believe that this NHL was resistant to this therapy, or developed resistance to it,
1 National cancer institute sponsored study of classification of nonHodgkin's lymphomas. S u m m a r y and description of a working formulation for clinical usage. The non-Hodgkin's lymphomapathologic classification project. Cancer 1982; 49: 2112-2135. 2 Ioachim IlL, Dorsett B, Cronin W, Maya M, Wahl S. Acquired immunodeficiency syndrome associated lymphomas: clinical, pathologic immunologic, and viral characteristics of 111 cases. Hum Pathol 1991; 22: 6 5 9 - 6 7 3 . 3 Garavelli PL, Azzini M. Leucosi in corso di infezione da HIV. Minerva Meal 1988; 79: 1 0 5 - 1 0 7 . 4 Gold ]E, Babu A., Penchaszadeh V, Castella A, Ghali V, Zalusky R. Hybrid acute leukemia in an HIV-antibody-positive patient. Am J Hematol 1989; 30: 2 4 0 - 2 4 7 . 5 Mansberg R, Rowlings PA, Yip MY, Rozenberg MC. First and second complete remission in a HIV positive patient following remission induction therapy for acute non-lymphoblastic leukaemia. Aust NZJ Med 1991; 21: 55-57. 6 Monfardini S, Vaccher E, Pizzocaro G, et al. Unusual malignant t u m o u r s in 49 patients with H1V infection. AIDS 1989; 3: 449-4:52. 7 Murthy AR, Ho D, Goetz MB. Relationship between acute myelomonoblastic leukemia and infection due to h u m a n immunodeficiency virus. Rev Infect Dis 1991; 13: 2 5 4 - 2 5 6 . 8 Napoli VM, Stein SF, Spira T], Raskin D. Myelodysplasia progressing to acute myeloblastic leukemia in a n HTLV-III virus-positive homosexual m a n with AIDS related complex. Am ] Clin Pathol 1986; 86: 7 8 8 - 7 9 1 . 9 Peters BS, Matthews J, Gompels M, Hartley JC, Pinching AJ. Acute myeloblastic leukaemia in AIDS. AIDS 1990; 4: 4 3 6 7 - 4 3 6 8 . 10 Puppo F, Scudeletti M, Murgia L, et al. Acute myelomonocytic leukaemia in an HIV-infected patient. AIDS 1992; 6: 1 3 6 - 1 3 7 . 11 Rivers JK, Laubenstein L], Postel AH. Acute monocytic leukaemia in a HIV-seropositive man. Clin Exp Dermatol 1992; 17: 2 0 3 - 2 0 5 . 12 Wijermans PW, Ten Kate RW. Successful chemotherapy for acute myeloid leukemia in HIV-infected patients. Eur ] Haematol 1990; 44: 1 3 6 - 1 3 8 . 13 Willumsen L, Ellengaard J, Petersen B. HIV infection in acute myeloblastic leukemia: a similar case. Am J Cltn Pathol 1987; 88: 536-537. 14 Dufour P, Mors R, Lamy T et al. L'association idarubicine aracytine h a u t e dose: u n n o u v e a u traitement de rattrapage des lymphomes malins n o n hodgkiniens refractaires ou en rechute. XII)h congress of the french society of hematology, Strasbourg 1993 June 1-3. 15 Spina M, Tierell U. H u m a n immunodeficiency virus as a risk factor in miscellaneous cancers. Curr Opin Oncology 1992; 4: 9 0 7 - 9 0 1 .
CASE REPORT
Acute Myelogenous Leukaemia followed by Non-Hodgkin's Lymphoma in a Patient with AIDS Christian Rabaud 1, Vdronique Dorvaux 2, Thierry May 1, Jean Francois Paitel 2, Brigitte Witz 2, Pierre Lederlin 2 and Philippe Canton 1 Departments of 1Infectious and Tropical Diseases and 2Internal Medicine and Haematology, CHU Nancy, France Accepted for publication 24 November 1994
Introduction B cell non-Hodgkin's lymphoma (NHL) is a well known complication of those infected with HIV. Acute myelogenous leukaemia (AML) associated with HIV infection, however, seems to be extremely rare. To our knowledge, we report the first patient with AIDS who developed these malignancies during the same year.
Case Report In 1987, HIV infection was diagnosed in a 30-year-old homosexual man. In February 1992 he presented with cytomegalovirus (CMV) retinitis and was treated with ganciclovir at an initial dose of lOmg/kg/day for 3 weeks, followed by 5 mg/kg/day for 3 months, zidovudine 600mg/day and cotrimoxazole 480mg/day. In April 1993, the patient was readmitted to the hospital with weight loss and progressive weakness. Physical examination only revealed paleness and cachexia. CD4 + lymphocyte count was below 50 x 106/1. Laboratory findings show pancytopenia (haemoglobin (Hb) 4 g/dl; WBC count 9.4: x 109/1 with 40% blood myeloblasts; platelets 10 x 109/1). Bone marrow films revealed 60% myeloblasts (M2, French-American-British cooperative group classification (FAB)). Blast cell histochemical and surface marker findings were typical of myeloblastic leukaemia: positive for peroxidase, CD33 99%, CD15 98%, CD14 97%. Cytogenetic analysis was inconclusive (no mitoses). Epstein Barr virus serology was positive and was not in favour of a recent infection (VCA IgG: +; VCA IgM: - ; EBNA IgG:+). Following induction therapy with
Address correspondence to: Dr Christian Rabaud, Service de Maladies Infectieuses et Tropicales, CHU de Nancy - H6pitaux de Brabois, F - 5 4 5 1 1 Vandoeuvre Cedex, France.
0163~t453/95/040069 +02 $ 0 8 . 0 0 / 0
cytarabine 200 mg/m 2 from day 1 to day 7 and idarubicin 8 mg/m 2 from day 1 to day 5 (May 14), complete remission (CR) was achieved. On July 12 he received consolidation therapy of cytarabine 3 g/m 2 twice daily from day 1 to day 4 and idarubicin lOmg/m 2 from day 5 to day 6. After partial recovery of drug-induced cytopenia (Hb 10 g/dl; WBC 3.2 x 109/1; platelets 63 x 109/1), he developed fever. Chest X-ray showed nodular lesions in the base of both lungs. Broncho-alveolar lavage and biopsy were negative except for CMV. As the lung lesions continued to progress (Figure 1), thoracotomy was performed which revealed a stage IV non-Hodgkins lymphoma (G, Working Formulation1). After two courses of chemotherapy (October 10 and November 12; cyclophosphamide: 750 mg/m 2 day 1; half dose of adriamycin: 2 5 m g / m 2 day 1; vincristine 1.4mg/m 2 day 1; prednisolone 40 mg/m 2from day 1 to day 5) with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), the nodular lesions decreased in size. At the same time, CMV retinitis reappeared and because of persistent cytopenia was treated with foscarnet. (Hb 6g/dl; WBC 0.9 x 109/1; platelets 25 x 109/1). Bone marrow films revealed no myeloblasts. On December 12, the patient died suddenly from air embolism due to an accidental leak of air into the central venous catheter. Post mortem examination revealed decrease in lung NHL lesions: only a single i cm lesion remained and histopathological examination confirmed the presence of lymphoma cells.
Discussion Non-Hodgkins lymphoma occurs frequently in patients with AIDS.2 Only 14 cases of AML in such patients have previously been reported. 3-13 Most frequent were M4 (FAB) (five patients) 4'7'9'1° followed by M2 (FAB) (four © 1995 The British Society for the Study of Infection
70
Acute Myelogenous Leukaemia and that m u c h of the evolution of the NHL occurred after the initiation of this AML therapy. Despite resistance of NHL to cytarabine and idarubicin, cyclophosphamide efficacy remained. The CHOP regimen seems to remain effective for managing NHL in these patients. Much data confirms that malignancies occur more frequently in patients with AIDS t h a n in the general population. 1~ There is no recorded data about secondary malignancies in such patients probably due to their short survival time.
Acknowledgements The authors t h a n k Dr W Canada for his contribution to the manuscript.
References
Figure 1. Non-Hodgkin's l y m p h o m a nodular lesions in both lungs. Chest X-rays: September 22 nd 1993.
patients). 3'6'8'12At least five patients s-7'1°'12 received aggressive induction chemotherapy, three were treated with the protocol cytosine arabinoside for 7 days with daunorubicin for 3 d a y s Y '1° These five patients were all in complete remission with survival rates ranging from 8 - 2 2 + months. In spite of AIDS, our patient tolerated chemotherapy well and about 7 months remission was achieved before his death. As previously reported, s-7'1° we concluded that aggressive chemotherapy was relatively well tolerated in those who were HIV seropositive and patients with AIDS who developed AML, and that complete recession of AML could be achieved. To our knowledge, this is the first case of non-Hodgkins l y m p h o m a diagnosed after AML in a patient with AIDS. The interval between the two diagnoses was 4 months. The delay between AML treatment and the onset of NHL, however, did not suggest a secondary drug-induced NHL. Because this patient's NHL presented within a few months of AML chemotherapy, we think it was already developing when AML therapy was started. Efficacy of the AML therapy used for this patient had previously been proved against high grade NHL. 14 We believe that this NHL was resistant to this therapy, or developed resistance to it,
1 National cancer institute sponsored study of classification of nonHodgkin's lymphomas. S u m m a r y and description of a working formulation for clinical usage. The non-Hodgkin's lymphomapathologic classification project. Cancer 1982; 49: 2112-2135. 2 Ioachim IlL, Dorsett B, Cronin W, Maya M, Wahl S. Acquired immunodeficiency syndrome associated lymphomas: clinical, pathologic immunologic, and viral characteristics of 111 cases. Hum Pathol 1991; 22: 6 5 9 - 6 7 3 . 3 Garavelli PL, Azzini M. Leucosi in corso di infezione da HIV. Minerva Meal 1988; 79: 1 0 5 - 1 0 7 . 4 Gold ]E, Babu A., Penchaszadeh V, Castella A, Ghali V, Zalusky R. Hybrid acute leukemia in an HIV-antibody-positive patient. Am J Hematol 1989; 30: 2 4 0 - 2 4 7 . 5 Mansberg R, Rowlings PA, Yip MY, Rozenberg MC. First and second complete remission in a HIV positive patient following remission induction therapy for acute non-lymphoblastic leukaemia. Aust NZJ Med 1991; 21: 55-57. 6 Monfardini S, Vaccher E, Pizzocaro G, et al. Unusual malignant t u m o u r s in 49 patients with H1V infection. AIDS 1989; 3: 449-4:52. 7 Murthy AR, Ho D, Goetz MB. Relationship between acute myelomonoblastic leukemia and infection due to h u m a n immunodeficiency virus. Rev Infect Dis 1991; 13: 2 5 4 - 2 5 6 . 8 Napoli VM, Stein SF, Spira T], Raskin D. Myelodysplasia progressing to acute myeloblastic leukemia in a n HTLV-III virus-positive homosexual m a n with AIDS related complex. Am ] Clin Pathol 1986; 86: 7 8 8 - 7 9 1 . 9 Peters BS, Matthews J, Gompels M, Hartley JC, Pinching AJ. Acute myeloblastic leukaemia in AIDS. AIDS 1990; 4: 4 3 6 7 - 4 3 6 8 . 10 Puppo F, Scudeletti M, Murgia L, et al. Acute myelomonocytic leukaemia in an HIV-infected patient. AIDS 1992; 6: 1 3 6 - 1 3 7 . 11 Rivers JK, Laubenstein L], Postel AH. Acute monocytic leukaemia in a HIV-seropositive man. Clin Exp Dermatol 1992; 17: 2 0 3 - 2 0 5 . 12 Wijermans PW, Ten Kate RW. Successful chemotherapy for acute myeloid leukemia in HIV-infected patients. Eur ] Haematol 1990; 44: 1 3 6 - 1 3 8 . 13 Willumsen L, Ellengaard J, Petersen B. HIV infection in acute myeloblastic leukemia: a similar case. Am J Cltn Pathol 1987; 88: 536-537. 14 Dufour P, Mors R, Lamy T et al. L'association idarubicine aracytine h a u t e dose: u n n o u v e a u traitement de rattrapage des lymphomes malins n o n hodgkiniens refractaires ou en rechute. XII)h congress of the french society of hematology, Strasbourg 1993 June 1-3. 15 Spina M, Tierell U. H u m a n immunodeficiency virus as a risk factor in miscellaneous cancers. Curr Opin Oncology 1992; 4: 9 0 7 - 9 0 1 .