Correspondence
Correction
Case 37-1994: Juvenile Chronic Myelogenous Leukemia
N Engl J Med 1995; 332:540-541February 23, 1995
- Article
To the Editor:
The case report in the October 13 issue1 describes a newborn boy with juvenile chronic myelogenous leukemia that was diagnosed on the basis of “an open-liver biopsy, which revealed an extensive . . . infiltrate composed of immature-appearing mononuclear cells . . . having reactivity for myeloperoxidase . . . and lysozyme.” In our view, this diagnostic procedure was potentially dangerous for the patient and adds little information. In fact, the diagnosis could have been made by assessing the proliferation of the patient's granulocyte–macrophage progenitors in vitro.
In patients with juvenile chronic myelogenous leukemia, the peripheral-blood granulocyte–macrophage progenitors proliferate in vitro in the absence of exogenous granulocyte–macrophage colony-stimulating factor (GM-CSF), even when the cells are plated at very low densities.2 In these patients, the growth is due to a striking hypersensitivity of granulocyte–macrophage colony-forming units (CFU-GM) to GM-CSF alone3 and not to granulocyte colony-stimulating factor (G-CSF), as mistakenly stated in the Case Records.1
Spontaneous growth of CFU-GM depends on the presence of a small amount of GM-CSF produced by monocytes or macrophages, since the depletion of adherent cells abrogates this abnormal growth pattern. Thus, a simple clonogenic assay of the fraction of mononuclear cells derived from peripheral blood could have provided sufficient data, together with the clinical and laboratory findings, which included increased serum muramidase (lysozyme) levels, to establish the diagnosis of juvenile chronic myelogenous leukemia; this assay could also have been used to monitor remission.
3 ReferencesFranco Locatelli, M.D.
Patrizia Comoli, M.D.
Vittorio Rosti, M.D.
University of Pavia, 27100 Pavia, Italy1
Case Records of the Massachusetts General Hospital (Case 37-1994). N Engl J Med 1994;331:1005-1012
Full Text | Web of Science | Medline2
Estrov Z ,Grunberger T ,Chan HS ,Freedman MH . Juvenile chronic myelogenous leukemia: characterization of the disease using cell cultures. Blood 1986;67:1382-1387
Web of Science | Medline3
Emanuel PD ,Bates LJ ,Castleberry RP ,Gualtieri RJ ,Zuckerman KS . Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 1991;77:925-929
Web of Science | Medline
Author/Editor Response
The discussants reply:
To the Editor: Locatelli et al. question the use of liver biopsy to make a diagnosis of juvenile chronic myelogenous leukemia in our patient. Since we are fully aware that such a diagnostic approach is unusual, we thank Dr. Locatelli and his colleagues for the opportunity to make clear that in this particular case, such a biopsy was both appropriate and necessary.
In the weeks preceding the liver biopsy, immunophenotyping of bone marrow aspirate as well as peripheral blood was nondiagnostic for any leukemic process, as were the findings on examination of two bone marrow aspirates and two bone marrow biopsy specimens. As noted in the case presentation, an aggressive workup continued. The liver biopsy was considered only when, over a period of a few days, serious respiratory distress developed as a result of rapidly progressing hepatosplenomegaly. A liver biopsy and a further bone marrow aspiration were performed at virtually the same time in order to establish the diagnosis of juvenile chronic myelogenous leukemia and exclude the possibility of primary liver disease. During this period the leukocyte count had risen from approximately 25,000 per cubic millimeter to 50,000 to 73,000 per cubic millimeter. When the biopsy indicated juvenile chronic myelogenous leukemia, systemic chemotherapy with daunorubicin and cytarabin was promptly instituted, with a rapid reduction in the burden of proliferating myeloid cells and alleviation of the respiratory compromise.
A clonogenic assay of mononuclear cells derived from peripheral blood can indeed confirm a diagnosis of juvenile chronic myelogenous leukemia. Such an assay, however, at best takes one to two weeks, especially if one seeks to measure sensitivity to GM-CSF in addition to spontaneous proliferation. The rapid progression of leukocytosis and hepatosplenomegaly in our patient rendered a clonogenic assay useless for diagnostic purposes.
Eric F. Grabowski, M.D., Sc.D.
David H. Ebb, M.D.
William S. Ferguson, M.D.
Massachusetts General Hospital, Boston, MA 02114Author/Editor Response
As pointed out by Locatelli et al., peripheral-blood hematopoietic progenitors are hypersensitive to GM-CSF and not to G-CSF, as erroneously reported in my case discussion. In studies by Gualtieri et al.1 and Emanuel et al.,2 neutralizing antibodies to GM-CSF but not to G-CSF significantly reduced the spontaneous proliferation of hematopoietic progenitors obtained from patients with juvenile chronic myelogenous leukemia. These studies clearly indicate the part played by GM-CSF in this disorder. I thank Dr. Locatelli and his colleagues for affording me the opportunity to correct the record.
2 ReferencesRobert I. Parker, M.D.
State University of New York at Stony Brook, Stony Brook, NY 11794-81111
Emanuel PD ,Bates LJ ,Zhu SW ,Castleberry RP ,Gualtieri RJ ,Zuckerman KS . The role of monocyte-derived hemopoietic growth factors in the regulation of myeloproliferation in juvenile chronic myelogenous leukemia. Exp Hematol 1991;19:1017-1024
Web of Science | Medline2
Emanuel PD ,Bates LJ ,Castleberry RP ,Gualtieri RJ ,Zuckerman KS . Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 1991;77:925-929
Web of Science | Medline
