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1466 Part X: Malignant Myeloid Diseases Chapter 89: Chronic Myelogenous Leukemia and Related Disorders 1467

crisis in the first year of the chronic phase, or who delay transplantation Epidemiology
for other reasons, transplantation remains the best hope for long-term Most patients with CMML are older than age 50 years, the median age
survival if a histocompatible donor is available. 832,833 Relapse of acceler- is approximately 72 years, and approximately 90 percent of patients are
ated phase after allogeneic stem cell transplantation has responded to older than age 60 years at the time of diagnosis. Occasional cases have
904
897
infusion of donor cytotoxic T lymphocytes. The use of TKIs before been reported in older children and younger adults. Men are affected
allogeneic stem cell transplantation for patients in advanced phases of more frequently than women (approximately 2:1). 904–906 An evaluation
disease may favorably improve transplantation outcomes, especially of exogenous factors that might increase the incidence of CMML, did
when MCyR occurs before transplantation. 898 not find an association with benzene or other occupational or non-
occupational risk factors. 907
Autologous Hematopoietic Stem Cell Transplantation The disease may occur following therapy for an unrelated malig-
Autografting in the accelerated phase or blast crisis, either with stem nancy, most commonly lymphoma, breast, or prostate cancer. The prior
cells collected during chronic phase or with mobilized Ph chromosome– therapy was radiation, combined radiation and chemotherapy, or che-
negative progenitor cells collected upon cell rebound after intensive motherapy, alone. The median time of onset of CMML was 6 years. 908
chemotherapy, has resulted in apparent prolonged remission in some
patients, but this procedure is rarely used in advanced disease because Clinical Findings
of the high rate of relapse. Whether Ph chromosome–negative cells Signs and Symptoms The onset usually is insidious, and weakness,
899
collected during imatinib therapy have the same potential is unknown. infection, or exaggerated bleeding may bring patients to medical atten-
tion. 905,906 Hepatomegaly and splenomegaly occur in approximately
Splenectomy 50 percent of patients. Leukemia cutis occurs in a small proportion of
Splenectomy may be performed for palliation of painful splenic infarc- patients and the skin cellular infiltrate is usually has a monocytic pheno-
tions or hemorrhage. However, the complication rates are high, and the type: CD45, CD68, and lysozyme positive by immunostaining. Immune
procedure performed in this setting should be avoided if possible. 900 manifestations, such as vasculitis, pyoderma gangrenosum, immune
cytopenias, and connective tissue diseases, may occur in coincidence
COURSE AND PROGNOSIS with CMML. 909
The accelerated phase of CML generally is very poorly responsive or Blood and Marrow Findings The disease is characterized by
9
910
refractory to treatment and is a morbid state that can be fatal in weeks anemia and blood monocytosis greater than 1 × 10 /L. The white
to months in all but a few patients who undergo a successful stem cell cell count may be decreased, normal, or moderately elevated. In one
transplant from a histocompatible donor. Patients with myeloid blast study of 275 patients, the range in 247 informative patients was 0.9 to
904
9
crisis have a median survival of approximately 6 months, whereas 160 × 10 /L. Occasional patients, however, may have hyperleukocytosis
9
patients with lymphoid blast crisis have a median survival of approx- with total white cell counts of 250 to 300 × 10 /L associated with respira-
911
imately 12 months. 887–901 In the earliest study of imatinib in blast crisis, tory insufficiency resulting from pulmonary leukostasis. Promono-
patients with myeloblastic crisis had a slightly longer median survival cytes and monocytes are present in blood and may have dysmorphic
(approximately 5 months) than patients with lymphoid blast crisis plus features. Immature granulocytes (promyelocytes and myelocytes) may
Ph chromosome–positive ALL (3 months). The results are poor in either be present in the blood. Blood myeloblasts are absent in approximately
case. A worse survival was seen with abnormalities of chromosome 17, 75 percent of patients or, when present, usually do not exceed 10 per-
other superimposed translocations, or a high percentage of abnormal cent of total white cells. Most patients have thrombocytopenia, but nor-
9
metaphases. Severe cytopenias from repeated courses of cytotoxic mal or elevated platelet counts may occur (range: 3.0 to 1385 × 10 /L
902
904
therapy contribute to infections, hemorrhage, and organ dysfunction, among 227 patients in one series). Eosinophilia may be so prominent
especially liver and kidney dysfunction. Opportunistic infections with in occasional cases that the designation chronic eosinophilic leukemia
905,906,912
herpes viruses, cytomegalovirus, or fungi often supervene. The addition may be appropriate.
of imatinib or other TKI therapies has made only a small difference in The marrow is hypercellular as a result of granulomonocytic
long-term outcome, although formal studies of combinations of che- hyperplasia; the dominant cells are early myelocytes. Blasts cells are 1
motherapy and imatinib at a higher dose (600 mg/day) have not been to 4 percent in about two-thirds of patients and are from 5 to 19 percent
904
completed, and the results of trials with second-generation TKIs are in one-third of cases. The proportion of promyelocytes is increased.
anticipated. Promonocytes and monocytes also are increased in number. Distinc-
tion between poorly granulated myelocytes and promonocytes with pri-
mary granules can be difficult. Macronormoblasts and hypersegmented
RELATED CLONAL MYELOID DISEASES or hyposegmented, often bilobed (acquired Pelger-Huët anomaly),
neutrophils may be evident but are more frequent in cases with lower
WITHOUT THE BCR REARRANGEMENT white cell counts. Despite thrombocytopenia, megakaryocytes usually
are present in the marrow. Microvessel density is increased in the mar-
In addition to classic CML with the BCR-ABL1 fusion gene, there are row, and myelomonocytic cells contain cytoplasmic mRNA for VEGF
several other chronic myeloid leukemias which are listed in Table 89–9.
and membrane VEGF receptors. 912,913 In vitro colony studies suggest that
autocrine stimulation of cell growth by VEGF may occur. “Spontane-
CHRONIC MYELOMONOCYTIC LEUKEMIA ous” cluster/colony growth of granulocyte-monocyte colony-forming
This leukemia is part of the spectrum of clonal myeloid diseases that cells occurs in vitro. The spontaneous growth may result from autocrine
may have findings that simulate CML. In the past, when rigorous cri- or paracrine production of GM-CSF, based on anti–GM-CSF inhibition
teria for the diagnosis of CML were not applied, CMML was among of colony growth. 914
a heterogenous group of related diseases that sometimes were referred Cytogenetic and Genetic Findings Patients with CMML have
to as Ph chromosome–negative CML. These diseases share the feature an approximately 35 percent frequency of chromosomal abnormalities.
of originating in the clonal expansion of a primitive multipotential Trisomy 8 and, to a lesser extent, monosomy 7 and −Y are the most
hematopoietic cell. 903 prevalent findings. A low–risk karyotype is either a normal pattern or

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