Mass effects caused by neoplastic infiltration, including bone pain resulting from marrow expansion and infiltration of the subperiosteum; generalized lymphadenopathy, splenomegaly, and hepatomegaly; and in T-ALL, complications related to compression of large vessels and airways in the mediastinum
Central nervous system manifestations resulting from meningeal spread, such as headache, vomiting, and nerve palsies
Despite its highly malignant natural history, pediatric ALL is one of the great success stories of oncology. With aggressive chemotherapy, about 95% of children with ALL obtain a remission, and 75% to 85% are cured. It is sobering http://ebooksmedicine.net
Fig. 12.14 Acutelymphoblasticleukemia(ALL).(A)Lymphoblastswithcondensednuclearchromatin,smallnucleoli,andscantagranularcytoplasm.
(B)and(C)showflowcytometryresultsfortheALLshownin(A).ThetumorcellsarepositivefortheBcellmarkersCD19andCD22;CD10(amarkerexpressedonasubsetofALLs),andTdT(aspecializedDNApolymerasethatisexpressedinpre-Bandpre-Tcells).(A,Courtesy of Dr. Robert
W. McKenna, Department of Pathology, University of Texas Southwestern Medical School, Dallas,Texas. BandC,Courtesy of Dr. Louis Picker, Oregon Health Science Center, Portland, Oregon.) to consider, however, that ALL remains the leading cause of cancer deaths in children, and that only 35% to 40% of affected adults are cured. Several factors are associated with a worse prognosis: (1) age younger than 2 years, largely because these tumors are genetically distinct, often being associated with translocations involving the MLL gene; (2) presentation in adolescence or adulthood; and (3) peripheral blood blast counts greater than 100,000. Favorable prognostic markers include (1) age between 2 and 10 years, (2) a low white cell count, and (3) hyperdiploidy. The molecular detection of residual disease after therapy also is predictive of a worse outcome in both Band T-ALL and is being used to guide therapy.
Although most chromosomal aberrations in ALL alter the function of transcription factors, the t(9;22) instead creates a fusion gene encoding a constitutively active BCR-ABL tyrosine kinase (described later under chronic myeloid leukemia). Treatment of t(9;22)-positive ALLs with BCR-ABL kinase inhibitors in combination with conventional chemotherapy is highly effective and has improved the outcome for this subtype of B-ALL in both children and adults. Tests to identify other “targetable” mutated tyrosine kinases in ALLs lacking BCR-ABL are under development. The outlook for adults with ALL remains guarded, in part because of differences in the molecular pathogenesis of adult and childhood ALL, and also because older adults cannot tolerate the intensive chemotherapy regimens that are curative in children.
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially identical, differing only in the extent of peripheral blood involvement. Somewhat arbitrarily, if the peripheral blood lymphocyte count exceeds 5000 cells/µL, the patient is diagnosed with
CLL. Most cases fit the diagnostic criteria for CLL, which is the most common leukemia of adults in the Western world. By contrast, SLL constitutes only 4% of NHLs. For unclear reasons, CLL/SLL is much less common in Asia.