Chemotherapy for minimally differentiated acute myeloid leukemia (AML-M0)

Summary With the objective of establishing the optimal therapy for minimally differentiated acute myeloid leukemia (AML-M0), we examined the therapeutic results of five AML-M0 cases and reviewed the literature. In a series of 63 patients with newly diagnosed acute leukemia who were admitted to the Main Hospital of Nippon Medical School, five patients fit the criteria for AML-M0: negative myeloperoxidase (MPO) and Sudan black B reaction by light microscopy, negative for B- and T-lineage markers, and positive for myeloid markers. They were treated by means of AdVP [adriamycin, vincristine, and prednisolone (PSL)] therapy and/or BHAC-DMP [behenoylcytosine arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP), and PSL] therapy. The AdVP therapy was unsuccessful in the two patients who received it, while a complete remission (CR) was achieved with the BHAC-DMP therapy in three of four patients. Although one patient treated with BHAC-DMP did not achieve CR, his blasts were apparently sensitive to the therapy. In assessable cases in the literature where leukemic blasts were MPO-negative, myeloid marker-positive and B- and T-lineage marker-negative, CR was achieved in 54.5% and 44.4% with anti-acute myeloid leukemia therapy and anti-acute lymphocytic leukemia therapy, respectively. Five cases in the literature were treated with a chemotherapeutic regimen containing BHAC [or cytosine arabinoside (Ara-C)], DNR, and 6-MP, and all achieved CR. The regimen containing BHAC (or Ara-C), DNR, and 6-MP may be useful as induction chemotherapy for AML-MO.     

Complex karyotypic abnormality in an aged patient with acute myeloid leukemia (M 2)

A 74-year-old man was admitted on November 1986 because of general fatigue. His peripheral blood showed pancytopenia without immature cells since December 1985. Hematological data showed RBC 150 X 10(4)/microliter, PLT 7,000/microliter, WBC 12,000/microliter with 93.6% leukemic cells. The bone marrow smear revealed NCC 14.5 x 10(4)/microliter with 76% leukemic cells. The leukemic cells were characterized by faint staining with peroxidase stain and strong positivity for CD 13 antigen determined with immunoperoxidase method and flow cytometric analysis. The chromosomal analysis of tumor cells represented as follows: 44, XY, -3, -4, -9, -20, 2q+, 6p-, 7q-, 12q+, +2 mar. Although remarkable reduction of leukemic cells in peripheral blood was obtained one month after initiation of 19-days intravenous continuous infusion of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), he suffered from severe systemic candida infection with severe leukopenia and died. Not only advanced age but also complex karyotypic abnormality would contribute to failure of treatment in this case. The significance of complex karyotypic abnormality in acute non-lymphocytic leukemia in discussed based on the current literature.     

Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0)

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P- glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.     

Pseudomonas sepsis with ecthyma gangrenosum in an acute myeloid leukemia patient

A 56-year-old woman with acute myeloid leukemia had two rapidly growing necrotizing nodules with ulcer formation on her head after the first course of consolidation therapy. Clinical features corresponding to sepsis (e.g., fever) appeared following the development of the skin lesion. Pseudomonas aeruginosa was isolated from the blood as well as pus of the lesion. Based on these findings, a diagnosis of ecthyma gangrenosum was made. Treatment with ciprofloxacin and gamma-globulin dramatically improved the patient's clinical features. Since Pseudomonas sepsis with ecthyma gangrenosum is associated with a high mortality rate, it is important to start immediate treatment with appropriate antibiotics.     

Skin lesion in a patient with acute myeloid leukemia

We present the case of a 51‐year‐old man with acute myeloid leukemia who developed fevers with a skin lesion following the first cycle of induction chemotherapy. Skin biopsy showed evidence of invasive fungal infection. Cultures remained negative, but polymerase chain reaction on tissue detected Rhizopus oryzae complex. The patient was started on liposomal amphotericin B and underwent surgical debridement. He was switched to posaconazole, with plans for allogeneic hematopoetic stem cell transplant in the future.     

Second complete remission in an elderly patient with acute myeloid leukemia retreated with decitabine

A 67-year-old man with acute myeloid leukemia (AML) was treated with low-dose decitabine. He achieved a complete remission (CR) after two cycles of therapy, and he remained in remission during 1 year of treatment. He developed recurrent AML after discontinuation of decitabine. He was retreated with decitabine and again achieved a CR, which has been maintained for 6 months. This case demonstrates that durable responses can occur upon retreatment with decitabine.     

Splenic actinomycotic abscess in a patient with acute myeloid leukemia

Actinomycosis is a gram-positive anaerobic bacterium. Actinomyces organisms are important constituents of the normal flora of mucous membranes and are considered opportunistic pathogens. The three major clinical presentations of actinomycosis include the cervicofacial, thoracic, and abdominopelvic regions. Actinomycosis infection in patients with febrile neutropenia is uncommon and actinomycosis splenic involvement in acute leukemia patients is very rare. We describe a man with acute myeloid leukemia and splenic actinomycotic abscess that developed after chemotherapy following prolonged neutropenia.     

Chronic systemic aspergillosis in a patient with acute myeloid leukemia

 Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis. Received: 13 November 1997 / Accepted: 11 February 1998     

Enterococcus gallinarum septicemia in a patient with acute myeloid leukemia

A 62-year-old male was admitted with complaints of fever and body weight loss. The patient was diagnosed as acute myeloid leukemia (M1) and chemotherapy was started. About 80 days after admission, the patient developed diarrhea with high fever. And E. gallinarum was isolated from the blood culture. We carried out PCR using primers for vanA, vanB and vanC in our E. gallinarum, and showed the existence of the vanC1. This organism should be considered as one of the possible pathogenes in the infectious complications of the immuno-compromized patient.     

Very early onset of an acute myeloid leukemia in an adult patient with B‐cell lymphoblastic leukemia

We report on a case of a 30‐year‐old male with acute B‐lymphoblastic leukemia (B‐ALL) with immunophenotype CD19⁺, CD22⁺, CD20⁺, CD10⁺, with aberrant expression of CD13 and CD117, and IgH gene rearrangements. Three months after treatment with GMALL‐2003 and Ida/FLAG protocols bone marrow showed predominance of blasts with myeloid morphology and phenotype MPO⁺, CD13⁺, CD33⁺, CD64⁺, CD15⁺, CD56⁺, EVI‐1 gene overexpression and lack of IgH rearrangements. The case is the first report of a very early emergence of myeloid leukemia during the induction treatment for B‐ALL in an adult patient. Different pathogenetic mechanisms are discussed – clonal evolution or selection, lineage switch or development of a de novo or therapy‐induced leukemia.     

CD 56-positive acute myeloid leukemia (AML-M 1) with t(16;21) (p11;q22) presenting an extramedullary tumor in the right breast at relapse

A 46-year-old woman was diagnosed as having acute myeloid leukemia (M 1) with translocation t(16;21) (p11;q22). The leukemic cells were positive for CD 13, CD 33, CD 34, CD 41, CD 56 and HLA-DR. After induction chemotherapy, the patient achieved complete remission (CR). However, 8 months later she relapsed with various additional chromosomal abnormalities. Although the patient achieved a 2nd CR after re-induction chemotherapy, the patient had extramedullary tumors in the right breast twice and relapse occurred frequently. The tumor cells were characterized by the same immunophenotypes and t(16;21) with additional 1 q trisomy. Although there was no evidence of hematological relapse, another type of 1 q trisomy was observed. Furthermore, an increase of abnormalities with 1 q trisomy was noted concomitant with re-increase in the number of blasts. The patient underwent allogeneic bone marrow transplantation (BMT), but she died from BMT complications. The case could have been a karyotype of t(16;21) with additional chromosomal abnormalities through consecutive approaches. Because of the high occurrence rate of relapse, we consider various additional chromosomal abnormalities and the expression of CD 56 as prognostic factors of this condition.     

Cedecea davisae bacteremia in a neutropenic patient with acute myeloid leukemia

Cedecea are the new members of Enterobacteriacea. Because of their inherent resistance to some antibiotics, the clinical response could be unpredictable making management of Cedecea infection in immunocompromised patients challenging. We report a case of acute myeloid leukemia with central line-related Cedecea bacteremia.