A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22)

Abstract

Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

Chromosome 16 abnormalities associated with myeloid malignancies

“…Arthur and Bloomfield (1983) and subsequently Le Beau et al (1983) observed that this group of patients appeared to have an improved survival compared with ANLL patients as a whole. This finding has been supported by data from other groups (Holmes et al, 1985;Larson et al, 1986) 0 1991 WILEY-LISS, INC.…”

“…CNS involvement is an uncommon complication of ANLL, reported in only 7-1 1% of cases (Stewart et al, 1981). However, it has been reported in the M4Eo subgroup at relapse in up to 35% of cases (Holmes et al, 1985) characteristically with mass lesions demonstrable on CT scanning (Glass et al, 1987). T h e incidence of 8% in our series is comparable with that of ANLL in general.…”

“…Abnormalities additional to those involving 16 have frequently been described in the literature. Larson et al (1986) described 6 patients with trisomy 22, 4 patients with trisomy 8, and 3 patients with del(7q) in addition to chromosome 16 abnormalities, and Holmes et al (1985) also reported trisomy 8 and trisomy 22 as frequent additions. Two of our patients had trisomy 22 and a further 2 had trisomy 9.…”

“…but an increased incidence of central nervous system (CNS) leukemia at relapse has also been described (Bernard et al, 1989;Holmes et al, 1985;Ohyashiki et al, 1988) indicating that modified treatment regimens may be required for this group. T o investigate the pathological and clinical features of patients with this type of myeloid leukemia, we undertook a retrospective study of patients whose cytogenetic analysis in our department had revealed one of the characteristic abnormalities of chromosome 16.…”

Isolated extramedullary relapse in acute myeloid leukemia: A retrospective analysis

“…Today extramedullary relapse terminates remission in 5-10% of patients [1][2][3][4]. Factors predisposing to IEMR include t(8;21), inv (16) and t(11q23) and FAB M4 and M5 morphologies [6][7][8][9][10]. In this study, the blasts of 7 of 13 patients had one of these cytogenetic abnormalities and morphology was FAB M4 or M5 in 11 of 16.…”