Acute leukemia following a previous malignancy: do acute lymphoid leukemia and acute myeloid leukemia have common risk factors?

INTRODUCTION: Within the framework of the GIMEMA Study Group, the characteristics of acute lymphoid leukemia and acute myeloid leukemia occurring in patients who have suffered a previous malignancy were studied. Assessment was also made of the clinical course, laboratory features and overall outcome of these conditions. MATERIALS AND METHODS: A four-year, multi-center retrospective study was conducted to evaluate the effect of treatment for previous hematological malignancy on the development of secondary leukemia. The study collected in the GIMEMA Archive of Adult Acute Leukemia 3934 new cases of acute leukemia (2964 AML, 901 ALL, 60 acute biphenotypic leukemia). Among these cases, data were evaluated from patients with a personal history of a previous malignancy, and included inquiring into demographic data, history of neoplastic diseases in the 1st degree relatives, type and treatment of the previous malignancy, latency until the development of a secondary acute leukemia diagnosis, laboratory features, treatment and outcome at the onset of secondary acute leukemia. RESULTS: Approximately 200 (5.1%) patients presented a previous malignancy. Twenty-one were affected by ALL and 179 by AML. The proportion of patients with secondary AML was higher than that of patients with secondary ALL (179/2964 vs 21/901, O.R. 2.69-95% C.I. 1.66-4.39, P<0.001). The median latency, from the onset of the previous malignancy to the development of secondary ALL was 27 months and to the development of secondary AML was 52 months (P<0.05). Furthermore, of patients who previously received chemotherapy more developed a second AML (66/127 sAML vs 5/21 sALL; O.R. 3.46-95% C.I. 1.10-11.56, P<0.01). CONCLUSION: In most cases, chemotherapy treatment for a previous malignancy can play a role in the development of secondary AML. In almost all cases of secondary ALL, the role of previous drugs does not appear to be relevant. On the basis of our analysis, performed systematically for the first time on a large adult series of acute leukemia, we conclude that in these patients a biological predisposition to cancer may be suspected.

Contemporaneous acute myeloid leukaemia and sarcoidosis. Report of three cases.

Three cases of contemporaneous acute myeloid leukaemia (AML) and sarcoidosis are described. The possible pathogenic mechanisms concerning their concurrent appearance are discussed: if sarcoidosis impaired T-cell response, it could perhaps predispose the development of AML; alternatively, the development of sarcoidosis during AML may be due to a reaction linked to a diffuse release of tumour antigens with a subsequent formation of a non-caseating granulomata.

Atypical Sweet's syndrome in a neutropenic patient with acute myeloid leukemia, secondary to a RAEB-T, simulating thrombophlebitis.

We report a rare case of a patient with acute myeloid leukemia following refractory anemia with excess of blasts transformed (RAEB-T) who presented a clinical picture suggestive of thrombophlebitis. The ultrasonographic procedure and the response to corticosteroid treatment suggest that this condition was compatible with an atypical Sweet's syndrome.

Splenic hemangiosarcoma. A case report.

Splenic hemangiosarcoma is a rare and aggressive tumor. Up to now, less than 150 cases have been reported. We describe a patient with a rapide course. The diagnosis of hemangiosarcoma was based on immunohistochemical tests (factor-VIII-associated antigen, CD31, CD34). Despite the improvement of diagnostic techniques, pathological examination and immunohistochemistry remain the only methods available for the diagnosis.

Case reports. Secondary prophylaxis with liposomal amphotericin B after invasive aspergillosis following treatment for haematological malignancy.

We report our recent experience with two cases of invasive pulmonary aspergillosis in patients who were both undergoing chemotherapy, one for acute myeloid leukaemia and the other for primary amyloidosis. Both patients had bad prognostic factors and were in very poor clinical condition, but both recovered from infection after a prolonged therapy with liposomal amphotericin B (AmBisome) without signs of toxicity.

Tunneling Schmorl's nodes in an elderly woman treated for acute lymphoblastic leukemia.

We present a 70-year-old woman with pre-B acute lymphoblastic leukemia in whom serial imaging studies showed the development of multiple vertebral collapse, and communicating superior and inferior Schmorl's nodes creating a longitudinal channel ("tunneling" Schmorl's nodes) through the anterior aspect of T12 to L3 vertebral bodies of her osteoporotic thoracolumbar spine. This was observed after achieving complete remission of the disease and during maintenance therapy. The finding is felt to be secondary to iatrogenic exacerbation of osteoporosis.

The incidence of secondary leukemias.

BACKGROUND AND OBJECTIVE: The term secondary leukemia is usually employed to indicate both forms of acute myeloid leukemia (AML) evolving from previous myelodysplasia and forms of acute leukemia developing after exposure to environmental or therapeutic toxins or radiation (therapy related). Secondary leukemias account for 10-30% of all AML. The majority of secondary leukemias resulting from the use of cytotoxic drugs can be divided into two well defined groups depending on whether the patient has received 1) alkylating agents or 2) drugs binding to the enzyme DNA-topoisomerase II. Alkylating agents related leukemias are very similar to post MDS leukemias being characterized frequently by a preleukemic phase, tri-lineage dysplasia, frequent cytogenetic abnormalities involving chromosomes 5 and 7 and a poor prognosis. Secondary leukemias related to therapy with topoisomerase II inhibitors are not preceded by a preleukemic phase and show frequently balanced translocations involving chromosome 11q23. Among therapy-related leukemias, AML is generally a second neoplasm, thus a predisposition to malignancy, independently from previous chemotherapy, cannot be excluded. This review article examines the incidence of all secondary AMLs and the risk of therapy-related leukemia in relation to the different primary malignancies and treatments. INFORMATION SOURCES: The authors have been working in this field, both experimentally and at clinical level, contributing original papers for many years. In addition, the material examined in this review includes articles published in journals covered by MedLine, reviews in journals with high impact factor and recent reports presented at the Secondary Leukemia. An Update Symposium held in Rome in November 1998. STATE OF THE ART AND PERSPECTIVES: The incidence of secondary leukemias is increasing because of aging of the population (MDS is more frequent in elderly people) and widespread and successful use of chemoradiotherapy in cancer patients. In the GIMEMA archive of adult acute leukemia (2,964 AML pts from June 1992 to June 1996) an antecedent hematologic disorder (AHD) and/or MDS was found in 8% of all patients (10% of 2,118 patients aged more than 45 years and in 4% of 848 patients aged less than 45). In this series of patients, 6% of all myeloid leukemias were therapy-related leukemia. Therapy-related leukemias are a major problem in patients treated for Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, polycythemia, breast cancer, ovarian carcinoma, or testicular carcinoma. In the GIMEMA archive more than 50% of patients with secondary AML have breast cancer, NHL, and HD. Alkylating agents, nitrosureas and procarbazine appear to have the highest leukemogenic potential. Furthermore aggressive chemotherapy and radiotherapy followed or not by hematopoietic stem cell infusion will produce a more and more prolonged survival but also a greater incidence of secondary AML. Assessment of the risk of secondary leukemia should become part of any therapeutic plan for cancer patients. Avoidance of drugs with more leukemogenic potential will produce a marked reduction of secondary AML.

Lymphoid blastic crisis in Philadelphia chromosome-positive chronic granulocytic leukemia following high-grade non-Hodgkin's lymphoma A case report and review of literature.

In this paper we describe a case of a 65-year old man with a lymphoid blastic crisis of a chronic granulocytic leukemia occurring seven years after a palatine tonsillar non-Hodgkin's lymphoma treated with chemotherapy and radiation therapy. Bone marrow cytogenetic study demonstrated the presence of the typical t(9;22)(q34;q11) and the molecular biology study showed the p210 rearrangement (b2a2). The patient died within a few months, unresponsive to any treatment. This is the first case, described in literature, of a secondary chronic granulocytic leukemia onset with a lymphoid blastic crisis. The authors report the case and a literature review.

Acute hemorrhagic leukoencephalitis in patients with acute myeloid leukemia in hematologic complete remission.

The authors describe the cases of three patients affected by acute myeloid leukemia, in complete remission, who rapidly developed neurologic symptoms leading to death. Neither clinical characteristics, nor radiological or microbiological procedures, allowed an etiological diagnosis of the neurologic syndrome. Post-mortem examination of the brain showed both macroscopic and microscopic findings compatible with acute hemorrhagic leukoencephalitis. The difficulty in distinguishing this entity from other CNS disease-related complications (e.g. leukemia infiltration, drug toxicity, hemorrhages) should not lead to an underestimation of the true incidence of this complication. We believe that with more attention to the possibility of this complication there would probably be both a greater possibility of collecting clinical informations about the real impact of this dramatic disease and a stronger hope of finding the right treatment for it.

PCR-restriction enzyme analysis for detection of Candida DNA in blood from febrile patients with hematological malignancies.

Blood samples were drawn daily from 72 patients who had hematological malignancies, neutropenia, and fever and who had failed to respond to broad-spectrum antibiotics. Each sample was used for conventional fungal blood cultures and for detection and identification of Candida DNA by a PCR method with subsequent restriction enzyme analysis (REA) recently developed in our laboratory. The PCR method was able to detect five CFU of Candida spp. per ml of blood, and subsequent REA of the amplicons allowed the identification of the Candida species most commonly implicated in cases of candidiasis. Thirty-one patients were PCR-REA positive, and four of these patients were also culture positive. The ultimate diagnosis for 13 of these patients and 1 patient who was PCR-REA negative was disseminated candidiasis (confirmed by clinical data, multiple cultures, histology, autopsy, and/or ultrasonographic evidence of hepatosplenic candidiasis). The molecular method is significantly more sensitive than conventional fungal blood cultures and has a high negative predictive value (97.5%) for the development of disseminated candidiasis in neutropenic patients.

Retrospective study of candidemia in patients with hematological malignancies. Clinical features, risk factors and outcome of 76 episodes.

A retrospective study of 76 episodes of candidemia in 73 patients with underlying hematological malignancy, from 1988 until 1997, has been conducted to evaluate the clinical characteristics and to ascertain the variables related to the onset and the outcome of candidemia. The most frequent malignancy was acute myeloid leukemia (29 episodes). Candidemia developed mainly during aplasia in patients refractory to chemotherapy (42%). In 65 episodes (86%) the patients were neutropenic (ANC <1 x 10(9)/l) before the candidemia diagnosis for a median time of 13 d, and in 53 episodes (70%) at microbiological diagnosis of candidemia ANC was <1 x 10(9)/l. Candida albicans was the most frequently isolated etiologic agent (31 episodes), but C. non-albicans species sustained the majority of candidemia. Seventeen candidemias developed during azoles prophylaxis. One month after the diagnosis of candidemia, 26 patients died. In 19 cases, death was attributable to candidemia. The case-control study demonstrated, at univariate analysis, that the colonization with Candida. spp. (p=0.004), antimycotic prophylaxis (p=0.01), presence of central venous catheter (p=0.01), neutropenia (p=0.002), and the use of glycopeptide (p=0.0001) increased the risk of candidemia. Using multivariate regression analysis only colonization with Candida spp. and the previous therapy with glycopeptide were associated with a significantly increased risk. Acute mortality, expressed by a cumulative probability of survival at 30 d from diagnosis of candidemia, was 0.67 (95% C.I. 0.55-0.77) and was significantly reduced in patients with neutrophils <1 x 10(9)/l when compared to those with neutrophils >1 x 10(9)/l (p at Mantel-Cox=0.029). Overall cumulative probability of survival at 1 yr was 0.38 (95% C.I. 0.27-0.49) and only the treatment with Amfotericin B significantly reduced the risk of death.

Acute myeloid leukemia in patients previously diagnosed with breast cancer: experience of the GIMEMA group.

OBJECTIVE: To evaluate in a multicenter retrospective study, the clinical and laboratory characteristics and the outcome of patients with acute myeloid leukemia (sAML) previously diagnosed with breast cancer (BC) among an adult acute leukemia population. PATIENTS AND METHODS: Between June 1992 and July 1996, 3934 new cases of adults with acute leukemia were recorded in GIMEMA Archive of Adult Acute Leukemia (2964 AML, 901 ALL, 69 acute leukemia expressing both myeloid and lymphoid surface markers). RESULTS: Two hundred patients (5.1%) presented with a history of previous malignancy (21 of them were affected by ALL and 179 by AML). Among sAML, 37 patients (29%) had a previous breast cancer. They consisted of 36 females and 1 male, median age 56 years, range 34-87. The median latency between the 2 malignancies was 54 months (range 5-379). Twenty-seven patients received chemo- and/or radiotherapy for breast cancer (7 only chemotherapy, 6 only radiotherapy, and 14 combined treatment). All patients were surgically treated but in 10 patients surgical debridement was the sole therapy for breast cancer. The drugs most frequently employed were alkylating agents (18 patients), topoisomerase II inhibitors (9 patients), antimetabolites (20 patients) (CMF, CEF and MMM combinations). At onset of sAML the median WBC count was 7.7 x 10(9)/l (0.8-153) and the median platelet count was 33.5 x 10(9)/l (3-305). Considering morphological features, FAB subtypes were 4 M0, 5 M1, 11 M2, 5 M3, 8 M4, 3 M5, and 1 M6. Cytogenetic study was performed on 28 patients and 12 of them presented abnormalities. It is noteworthy that chromosome 5 or 7 abnormalities (typically observed in those patients treated with alkylating agents) were present only in three cases. Thirty-four patients received chemotherapy for sAML, and twenty-five of them achieved a CR (74%), with a median duration of twenty-eight weeks (5-280+). The overall survival was 8 months (1-80+). DISCUSSION: The high number of sAML we observed in patients with a previous breast cancer, may be due to the fact that this malignancy is the most frequent neoplasm in women and by the high probability of cure with a consequent long disease-free survival. Our results suggest that the risk of sAML after recovery from breast cancer is increasing due to the rise in the number of patients cured from breast cancer, and in the future could be a relevant problem for haematologists.