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Clinical Science

Acute myeloid leukemia in patients infected with HIV-1

Aboulafia, David M.a; Meneses, Michellea; Ginsberg, Stevenb; Siegel, Martin S.c; Howard, Walter W.d; Dezube, Bruce J.e

Author Information



In patients infected with HIV, the majority of hematological malignancies are intermediate and high-grade B-cell non-Hodgkin's lymphomas [1]. A few cases of HIV-associated lymphoblastic leukemia have been reported. They are of the French–American–British (FAB) L3 type and share their clinical presentation, treatment, and prognostic features with Burkitt's lymphoma [2]. An increasing number of patients with HIV infection and monoclonal gammopathies of uncertain significance have also been identified, although only rarely do they progress to overt myeloma [3]. Myelodysplasia is also frequently noted in HIV infection, but evolution to acute myeloid leukemia (AML) is distinctly unusual. Between 1995 and 2000, five patients with AIDS and AML were cared for by us at three separate hospitals. The presentations of these patients are described and those of 42 HIV-infected patients who subsequently developed AML who were identified from a search of the literature on reported cases of AML in HIV-infected patients. Patients with pre-existing AML who acquired HIV infection from tainted blood or blood products during therapy for AML were not considered.

Subjects and Methods

Case reports

There were five patients treated in our group of hospitals.

Patient 1

A 61–year-old homosexual man was diagnosed with HIV infection and Pneumocystis carinii pneumonia in 1995. Laboratory tests were notable for a CD4 T lymphocyte count of 4 × 106 cells/l and an HIV viral load > 100 000 copies/ml. He subsequently began highly active antiretroviral therapy (HAART) consisting of indinavir, zidovudine and lamivudine and remained asymptomatic for the next 5 years. His CD4 cell count gradually rose to 118 × 106 cells/l, and his HIV viral load decreased to 3500 copies/ml.

In 2000, he sought medical attention for mild exertional dyspnea, increasing fatigue, and weight loss of 5 lb (2.3 kg). He had a white blood count (WBC) 4.3 × 109 cells/l (of which 45% was myeloblasts), platelets 166 × 109 cells/l, hematocrit 28%, and mean corpuscular volume 110 fl. Bone marrow biopsy revealed a hypercellular marrow packed with sheets of myeloblasts. Malignant cells expressed the immunophenotypic markers HLA-DR, CD11b, and CD13–15 but did not express CD34 or terminal deoxynucleotidyltransferase (TdT). Myeloblasts stained positively for myeloperoxidase (granulocytes). He was diagnosed with AML (M4) with a normal XY karyotype.

The patient received treatment with a standard AML induction regimen consisting of continuous infusion cytarabine (200 mg/m2 daily) for 7 days and bolus idarubicin (12 mg/m2 daily) for 3 days (regimen 7+3). He tolerated chemotherapy well and by day 10 his peripheral smear was free of circulating blasts. Response to therapy, however, was short lived, and a few days later leukemic cells were again noted on peripheral blood smear. On day 21, his WBC was 45 × 109 cells/l with 40% blasts and he declined further efforts to induce remission with chemotherapy. Hydroxyurea was used to control blast count. He survived an additional 7 months before succumbing to progressive leukemia.

Patient 2

In 1995, a 43-year-old male with a 7 year history of HIV infection sought medical attention for a tender right submandibular mass and a fever of 1 week's duration. He had previously been free of illness despite a CD4 cell count of only 15 × 106 cells/l. Laboratory studies included a WBC of 1.9 × 109 cells/l with 16% blasts. He was hospitalized and began intravenous antibiotics. A computed tomographic scan of the neck confirmed the presence of a 2 cm × 3 cm fluctuant mass, which was aspirated and yielded purulent material. Bone marrow biopsy demonstrated sheets of immature cells, which stained with Sudan Black B and myeloperoxidase. The immunophenotypic markers HLA-DR, CD11b, CD13–15, and CD33 were detected but not TdT and CD34. These findings were consistent with a diagnosis of AML (M2). He was offered induction chemotherapy but chose instead supportive care. Two months later he was rehospitalized with spiking fevers and a WBC of 1.5 × 109 cells/l, of which 74% were myeloblasts. He died 1 week later.

Patient 3

In 1995, a 34-year-old homosexual male with a history of multiple AIDS-related illnesses and a CD4 cell count of 14 × 106 cells/l presented with pancytopenia and hemoptysis. Several months earlier, he had been diagnosed with cytomegalovirus retinitis and was still receiving treatment with maintenance intravenous ganciclovir. His initial WBC was 20 × 109 cells/l with 30% monocytes and his platelet count was 11 × 109 cells/l. He complained of persistent headache and a computed tomographic scan of his head showed a subdural hematoma. Four days later he underwent an emergency splenectomy for refractory thrombocytopenia. The spleen measured 26 cm × 12 cm × 8 cm and weighed 1045 g. No nodules were apparent, and numerous macrophages with hemosiderin and platelet-derived material were present in the red pulp. There was no evidence of lymphoma, and special stains did not reveal an opportunistic pathogen, although occasional cells suspicious for leukemia were noted in the red pulp.

After surgery, his WBC increased to 80 × 109 cells/l with 65% monocytes but no myeloblasts. He remained thrombocytopenic. A bone marrow biopsy demonstrated 100% cellularity with abundant monoblasts. Cytochemical stains were negative for Sudan Black B and positive for non-specific esterase (monocytes). Immunophenotypic markers detected were CD11b, CD13–15 and CD33 but not TdT and CD34. These findings were consistent with a diagnosis of AML (M5). Because of the patient's multiple medical problems, hydroxyurea alone was offered for control of WBC levels. He died 1 week later. At autopsy, examination of the lungs revealed necrotizing aspergillosis, cytomegalovirus pneumonitis, and leukemic pneumonitis. Leukemic infiltrates also involved the central nervous system, the intestines and stomach, the liver, and the kidneys.

Patient 4

In October 1997, a 62-year-old homosexual male who had been HIV positive since 1990 complained only of fatigue. For 18 months he had been taking HAART consisting of zidovudine, indinavir, and lamivudine. His general examination was unremarkable, but laboratory studies included WBC 4.1 × 109 cells/l (2% neutrophils, 44% monocytes, 54% lymphocytes), hematocrit 24%, and 83 × 109 cells/l platelets. His CD4 cell count was 442 × 106 cells/l and his HIV viral load was < 400 copies/ml. He received a blood transfusion and stavudine was substituted for zidovudine. In December 1997, because of persistent pancytopenia and the presence of circulating myeloblasts (Table 1), a bone marrow biopsy was obtained. The aspirate was hypercellular and contained 95% myeloblasts. Cytochemical staining was positive for myeloperoxidase and negative for non-specific esterase. Immunophenotypic markers were CD11b, CD13, CD14 and CD33 with weak staining for TdT and CD34. He was diagnosed with AML (M1). He began standard induction chemotherapy consisting of regimen 7+3. Five days into the cytarabine infusion, the patient became febrile and a chest roentgenogram demonstrated bilateral pulmonary infiltrates. Cytarabine was discontinued and was replaced with etoposide (100 mg/m2 daily) by bolus infusion for 2 days. By day 24, the neutropenia, pulmonary infiltrates, and fever had resolved. No residual leukemia was seen on a bone marrow aspirate at day 30. Consolidation chemotherapy was not recommended. Six months later the patient's CD4 lymphocyte count was 396 × 106 cells/l and his HIV viral load was < 50 copies/ml.

Table 1
Table 1:
Acute myeloid leukemia and HIV infection.

In June 1999, the patient was again pancytopenic (WBC 1.7 × 109 cells/l, hematocrit 26%, and platelets 40 × 109 cells/l). A bone marrow biopsy demonstrated relapsed AML. He again received regimen 7+3 chemotherapy. On hospital day 14, a bone marrow biopsy was hypocellular. The patient remained in hospital for an additional 2 weeks and received intermittent blood and platelet support. Five weeks following reinduction chemotherapy, his WBC was 4.8 × 109 cells/l, hematocrit 34%, and platelets 173 × 109 cells/l. Eighteen months later, the patient remains in clinical remission.

Patient 5

In April, 1998, a 49-year-old woman with a history of transfusion-associated AIDS and chronic leukopenia, for which she took low-dose granulocyte colony-stimulating factor (G-CSF), underwent evaluation of thrombocytopenia. She had previously received multiple antiviral regimens, which were compromised by HIV viral resistance and/or drug intolerance. Initial laboratory studies included WBC 2.4 × 109 cells/l (58% neutrophils, 16% monocytes, 19% lymphocytes), hematocrit 34%, platelets 16 × 109 cells/l, CD4 cell count 56 × 106 cells/l, and HIV viral load 96 300 copies/ml. Bone marrow biopsy showed normocellular marrow with decreased myeloid precursors, erythroid hyperplasia and adequate numbers of megakaryocytes. After assorted special stains and cultures returned unremarkable, she was given intravenous immunoglobulin but her platelet count did not improve.

In October 1998, she complained of progressive fatigue and early satiety in the setting of low-grade fevers, night sweats, weight loss, and increasing mucosal blood loss. Her physical examination showed extremity petechiae and new-onset hepatosplenomegaly. She was pancytopenic (WBC 1 × 109 cells/l, hematocrit 27%, platelets 15 × 109 cells/l). At diagnostic laparotomy, a 1600 g spleen, which measured 21 cm × 15 cm × 13 cm, was removed. Microscopic examination of the spleen revealed an immature hematopoietic cell infiltrate most consistent with AML. Blasts, now seen on peripheral blood smear, were positive for CD33, CD13, and CD11c. Cytochemical stains were positive for myeloperoxidase and non-specific esterase. Follow-up bone marrow biopsy revealed acute myelomonocytic leukemia (M4) and cytogenetic studies were notable for the presence of monosomy 7 and a deletion in the long arm of chromosome 5.

Given her weakened medical condition and the poor control of her underlying HIV disease, she declined aggressive chemotherapy. Over the ensuing 4 months, she received hydroxyurea followed by thioguanine and etoposide for control of WBC but died from progressive leukemia.

Subjects in the literature

A MEDLINE, CancerLit, and AIDSLINE search with the keywords HIV, leukaemia, AML, AIDS, human, and myelodysplasia identified a total of 42 additional cases of AML among HIV-seropositive patients reported between 1981 and 2001 [4–31]. In each instance, HIV-seropositive patients with AML were communicated as isolated case reports from single institutions in medical journals and, rarely, as brief abstracts at medical meetings. The exceptions to these are the series of five patients presented here and obtained from three hospitals between 1995 and 2001; a multi-institutional survey carried out in nine French hospitals between 1985 and 1994, which provided limited information on 13 cases of HIV-associated AML [26]; and an Italian registry of unusual cancers in patients with HIV infection, in which a single case of HIV-associated AML was reported [24].

Two cases were reported on two separate occasions [14–16,27]. Importantly, patients with myeloid leukemia who had acquired HIV infection from tainted blood or blood products after receiving therapy for AML were not considered in this review [32].


Cases included in this analysis are described in Table 1.

Clinical aspects

Of the 47 patients identified as having HIV-associated AML, 39 were male [4–8,10–22,26,27,29–31], six were female [9,23,25,26], and in two reports the sex was not specified [24,28]. The median age at the time of AML diagnosis was 38 years (18–70). The principal risk behavior for HIV acquisition was sexual transmission (15 homosexual [5,7,8,12–17,22,27,33], one heterosexual [6,25], and two bisexual [7,30]), intravenous drug use in seven [4,6,9,11,19,20,29], and blood product transfusion in two [30]. In 20, the risk factor for HIV infection was not stated [10,18,21,23,24,26,28].

HIV infection was present for a median of 48 (7–180) months before a diagnosis of AML was established (35 patients). In eight, AML was diagnosed first and, because of an identified risk factor for HIV acquisition or the presence of an AIDS-defining illness, serotesting for HIV was performed at a follow-up evaluation [8,10,20,22,25,29]. One patient was diagnosed with HIV 4 months after AML [10], and for three patients, the duration prior to HIV diagnosis was not specified [12,18,24]. At time of AML diagnosis, the median CD4 cell count was 210 × 106 cells/l (range, 5–1200) for the 32 patients for whom this information was reported. Prior to 1995, quantitative methods for measuring serum HIV viral loads were not commercially available and consequently in only very recent reports is this information provided [21,30].

At presentation, leukocytosis was common, with a median WBC of 14 × 109 cells/l (range 0.6–256.6) in 29 patients. Most patients were also anemic and thrombocytopenic. Five patients, including patients 3 and 5, presented with pancytopenia but no circulating myeloblasts [6,8,22]. AML was diagnosed in each instance by bone marrow aspirate and biopsy. Extramedullary leukemic infiltrates at diagnosis or at relapse were frequently observed involving the spleen [4,16,20,26], skin [10–12,15,16,23,26,29], gingival [15], and testes [12]. In patient 3, widespread gastrointestinal, pulmonary, and central nervous system involvement was detected at autopsy examination, even though it was not suspected antemortem. Patient 5 was found to have splenic involvement, and only after splenectomy did myeloblasts appear in the peripheral blood smear.

Including patients 4 and 5, a total of six (13%) patients had cytopenias that were initially attributed to HIV or zidovudine [7,21,23]. One patient underwent a bone marrow biopsy for evaluation of neutropenia. He was diagnosed with refractory anemia in association with a monosomy 7 [21], received G-CSF treatment for 1 year, subsequently developed AML and died shortly thereafter. A second patient was treated with G-CSF for what was initially believed to be zidovudine-induced neutropenia [23]. Three months later, she developed leukemia cutis and 70% myeloblasts were detected on peripheral blood smear. G-CSF was discontinued and blast crisis and leukemic skin infiltrates resolved. This response was short lived and 3 months later AML recurred and she died from septic complications. Two additional patients presented with cytopenias that were initially attributed to zidovudine; in both instances, they died from complications of AML before chemotherapy was administered [7].

FAB M2 leukemia was reported in 15 patients [4,8,20,22,24,26], M4 in 14 [5,7,9,10,14,16,23,26,30], M5 in nine [6,10,11,15,16,26,31], M3 in two [19,26], M1 in four [17,18,26], M0 in one [30] and for two patients the FAB classification was not reported [21,28]. One female had biphenotypic leukemia with both lymphocytic and myelocytic markers, which indicated Burkitt's lymphoma/acute lymphoblastic leukemia (L3) and AML (M2) [25]. Together, M2 and M4 subtypes represented 64% (29/45) of reported cases, which is approximately double what might otherwise be expected in AML not associated with HIV infection [33].

Cytogenetic studies were reported in 16 patients [4,6,8,9,11,14,16–19,22,25,30,31]. Three patients had normal karyotypes, and 12 were associated with a wide variety of abnormalities including inversion 16, monosomy 7, and t(15;17). One patient with a complex karyotype had a preceding history over 10 years of polycythemia vera [30]. Six patients had abnormalities in chromosome 7 [4,6,16,17,21,25], a cytogenetic abnormality associated with myelofibrosis, myelodysplasia, and previous exposure to chemotherapy [34,35]. In three such instances, HIV-infected patients were initially diagnosed with non-Hodgkin's lymphoma, received alkylating agents and topoisomerase II inhibitors, and developed AML 16, 18 and 23 months, respectively, following their lymphoma diagnoses [17,31]. One intravenous drug user underwent a bone marrow biopsy for evaluation of pancytopenia and was diagnosed with refractory anemia with excessive blasts in transformation [4]. Shortly after, he developed M2 leukemia.

Only 2 of the 47 (4.3%) patients in this review were diagnosed with Kaposi's sarcoma [7,15,16]; five (10.6%) were diagnosed with non-Hodgkin's lymphoma. In two, lymphomas were diagnosed 2 and 6 months following the initiation of AML induction chemotherapy [13,26]. Three patients underwent successful lymphoma therapy but died of AML-related complications 2 and 10 years later [17,31]. One patient was initially diagnosed with cutaneous diffuse large B cell lymphoma of the cheek [11]. The tumor did not respond to lymphoma therapy, and only after further review was the diagnosis changed to leukemia cutis secondary to AML.

Treatment and prognosis

A total of 29 patients received standard AML induction chemotherapy. The most common regimen employed was regimen 7+3 [5,6,9,13,14,16,26,30,31]. Three patients received a combination of daunorubicin, cytarabine, and 6–thioguanine [10,12,20], and two patients received continuous infusion cytarabine for 5 days without concomitant anthracycline [17]. Two patients with M3 leukemia were initially treated with all-trans-retinoic acid [19,26], of whom one later underwent consolidation chemotherapy consisting of cytarabine and daunorubicin [19]. One patient received low-dose cytarabine (10 mg/m2 subcutaneously twice daily) followed by a low-dose cytarabine maintenance regimen [8].

Induction phase chemotherapy was surprisingly well tolerated. Five toxic deaths occurred, two from pulmonary aspergillosis [4,30], one from subarachnoid hemorrhage [12], one from catheter-related air embolus [13], and one from Candida glabrata fungemia [31]. Complete hematologic remission was reported in 26 of the 29 patients (83%), although the criteria used to assess response were not always stated and the results of restaging bone marrow biopsies or cytogenetic studies were rarely documented [5,6,8,9,10,13,14,16,17,19,20,24,26]. For example, two patients who were credited with complete hematologic remissions had persistent leukemic cutis [12,15].

A total of three patients underwent high-dose chemotherapy followed by autologous bone marrow reinfusion. The first such patient achieved a first remission of 13 months and a second remission of 11 months with standard induction chemotherapy [14]. At third relapse, he received high-dose chemotherapy consisting of busulfan (3 mg/kg daily for 4 days) and cyclophosphamide (50 mg/kg daily for 2 days). He survived for an additional 23 months with transfusion-dependent anemia and thrombocytopenia before dying of recurrent AML. Despite multiple cycles of chemotherapy, the patient maintained a CD4 cell count > 300 × 106 cells/l throughout much of his illness. Two additional patients received high-dose consolidation chemotherapy followed by autologous bone marrow reinfusion [26,28]. Detailed information regarding their clinical courses is lacking, although in each instance the patient appeared to have achieved a relatively durable response.

Median survival of the chemotherapy-treated patients was 7.5 months, compared with a median survival of 1 month (range, 2 days to 3 months) for 9 of the 12 patients [4,7,10,18,21–23,25,26,30,31] who did not receive induction chemotherapy and for whom this information was reported. A handful of patients have achieved long-term survival following several cycles of chemotherapy. Among single case reports, the patient with the longest disease-free survival was reported to be in complete remission 22 months after receiving low-dose cytarabine induction therapy followed by maintenance daily subcutaneous injections of cytarabine [8]. Despite a lack of long-term follow-up, relapses were reported in 14 of the 26 (54%) complete responders. The importance of long-term follow-up is illustrated by the report of a patient who was believed to be in complete remission at the time his case was first published [27], but who later relapsed after an 11–month remission [14].

In the only previously reported series that included more than two patients, Sutton and colleagues described in abstract form their experience in evaluating 13 patients with HIV-associated AML in France between 1985 and 1994 [26]. Of the 11 patients who were deemed medically stable for chemotherapy, 10 received an anthracycline plus cytarabine, and one was treated with all-trans-retinoic acid following a diagnosis of AML M3. Complete remissions were reported in 10 of 11 patients, and three were reported to still be alive at time of abstract publication after 42, 49 and 86 months, respectively; five relapsed and died at 2, 4, 10, 12 and 16 months, respectively.

A survival analysis was performed to address whether immune function had an effect on overall survival of patients. Log CD4 cell count was used as a predictor variable to model time to death or time to censoring. The log CD4 cell count was highly significant in this model (P = 0.005). Quantitatively, patients with a CD4 cell count < 200 × 106 cells/l had a median survival time of 7 weeks, while patients with a CD4 cell count ≥ 200 × 106 cells/l had a median survival of 7 months (there are 18 patients who had both CD4 cell count and time to death or censoring known and are included in this analysis). Eleven patients (36%) with CD4 cell counts < 200 × 106 cells/l survived greater than 6 months compared with seven (71%) with CD4 cell counts > 200 × 106 cells/l.


Laboratory investigations have sought to determine if there is more than a coincidental association between HIV infection and the subsequent development of AML, akin, for example, to that seen with human T cell leukemia virus type 1 (HTLV-1) and adult T cell leukaemia–lymphoma [36,37]. Murthy and colleagues isolated HIV from circulating myelomonoblasts obtained from an HIV-infected man with AML M4 [5]. Myelomonoblasts cultured without the addition of growth factors showed evidence of HIV replication by the presence of p24 antigen and reverse transcriptase activity in the supernatant of the cell culture. In contrast, Farber and associates co-cultured peripheral blood donor lymphocytes with leukemic monocytes from an HIV-seropositive man with AML M4eo but were unable to identify the presence of infectious viral particles [27]. Costello and colleagues also failed to detect HIV hybrid fragments in myeloblast DNA from an HIV seropositive patient with AML M5 [5].

The high incidence of AML in two disorders associated with chronic T cell abnormalities, severe combined immunodeficiency and the Wiskott–Aldrich syndrome, indicate that immunodeficiency states can be associated with AML [38]. Our report cannot prove such an association between HIV infection and AML, and broad-based epidemiological studies across various tumor registries do not suggest that such an association exists [24,39,40]. Additionally, in the Seattle Adult/Adolescent Spectrum of HIV-Related Diseases project, there were no diagnoses of AML in the 12 182 person-years of follow-up 1990–2000 [41]. However, it is noteworthy that patients infected with HIV are susceptible to a variety of cancers, including Kaposi's sarcoma, Hodgkin's and non-Hodgkin's lymphoma, and carcinomas of testes, anus and cervix [39]. As a number of patients with AIDS and non-Hodgkin's lymphoma survive their lymphatic malignancy or are exposed to other chemotherapy regimens and/or radiotherapy for non-AIDS-defining malignancies, they will be at risk for therapy-related AML [17,31]. Both alkylating agents and topoisomerase II inhibitors have been implicated in the pathogenesis of such AML. Exposure to medications including HIV nucleoside analogs [42] and cytostatic agents such as the ribonucleotide reductase inhibitor hydroxyurea [43] may also place HIV-infected patients at heightened risk for leukemic complications. As the number of agents used to treat HIV infection and its complications continue to grow, it will be important to determine if AML incidences increase longitudinally. Excluding our own series of five patients (three of whom received HAART), we were able to identify only a handful of cases of AML reported after 1996 when HAART became widely available [14,17,18,20,21,28,30]; consequently, continued reappraisal of this issue is in order.

In HIV-infected individuals, AML has been characterized by a predominance of FAB M2, M4, and M5. Assumptions regarding an etiopathological link between the AML subtypes and HIV infection must, however, be viewed in the context of the limited number of cases identified and from which percentages are derived. With this caveat in mind, we postulate several mechanisms by which HIV-1 can lead to the development of AML. During acute infection of CD4 cells by HIV-1, the potent trans-activator protein Tat is released extracellularly [44]. Tat plays a vital role in the process of angiogenesis; transgenic mice develop angioproliferative Kaposi's sarcoma-like lesions when the HIV tat is introduced into their germline [45]. Angiogenesis also plays a vital role in the pathogenesis of acute leukemias [46,47]. The potential role of Tat in the pathogenesis of leukemia is underscored by the ability of the basic domain of Tat to displace preformed basic fibroblast growth factor (bFGF) bound to heparan sulfate proteoglycans into a soluble form [48]. bFGF has been demonstrated by several groups to augment myelopoiesis directly via FGF receptors on myeloid progenitors [49,50]. Finally, HIV may alter the bone marrow microenvironment, making it more permissive to the growth of leukemic cells. HIV-1 is capable of infecting monocytes and macrophages. Such an infection could lead to an increase in DNA-binding activity of the NF-κB/rel transcription factor, which could activate the genes of cytokines putatively involved in leukemogenesis (e.g., G-CSF, granulocyte–macrophage colony-stimulating factor, and interleukin-6 [16,20,51]).

In HIV-infected individuals, AML has also been characterized by the occurrence of extramedullary leukemic infiltration reminiscent of extranodal disease in AIDS-related non-Hodgkin's lymphoma. Despite the presence of comorbid illnesses and uncertainty regarding how best to treat HIV disease, particularly prior to the HAART era, most patients reviewed here who were deemed sufficiently stable to receive AML induction chemotherapy tolerated the treatment well and achieved clinical complete remission. Prognosis for those with an antecedent history of AIDS, however, was dismal. In five instances a delay in diagnosis occurred because the cytopenia was presumed to be related to antiretroviral therapy. It is unclear whether prompt recognition of leukemia would have resulted in a better clinical outcome.

Following AML induction chemotherapy, the occasional favorable outcomes reported by some investigators, most notably Sutton et al. [26], may relate, in part, to several important immunological factors. Patients in that study had relatively early HIV infection (median CD4 cell count was 536 × 106 cells/l), and only four patients had CD4 cell counts < 200 × 106 cells/l. As in patients 2, 3, and 5 in our cohort (where patients presented with an antecedent history of advanced AIDS), the worst outcomes in the Sutton cohort were observed in the six patients with a pre-existing history of AIDS. Treatment was not deemed possible in two, chemotherapy failed in one, complete remission was short in two (2 and 4 months), and a subsequent lymphoma occurred in one patient.

In the HAART era, the incidence of Kaposi's sarcoma is declining, the incidence of non-Hodgkin's lymphoma is reaching a plateau [52],and the overall survival of patients with AIDS is improved dramatically [53]. As a result, the occurrence of malignancies not typically associated with HIV infection, especially those malignancies where the incidence increases with age (which includes AML), may become more prevalent as the HIV-infected population ages. Furthermore, three reported cases suggest that the time course for therapy-related malignancies in the setting of HIV infection may be markedly shorter than that for immunocompetent patients, where second malignancies usually occur 5–12 years after chemotherapy [17,31]. Paradoxically, if HIV-1 Tat does play a role in the development of AML, then more effective suppression of HIV replication may translate into fewer HIV-associated cases of AML. Consequently, as patients with HIV infection survive for longer periods through more effective antiretroviral therapies, it will become increasingly important to define the appropriate use of traditional and novel chemotherapeutic strategies and dose-intense regimens with options for bone marrow rescue.


We thank Susan Buskin, David Kerr, David Scadden, and Paul Weiden for careful review of this manuscript, and Arleen Sierra and Christine Jones for text preparation.


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HIV-1; AIDS; cancers; acute myeloid leukemia; chemotherapy; treatment

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