Page 1199 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 66 Acute Lymphoblastic Leukemia in Adults 1047

A B C
Fig. 66.8 BURKITT LEUKEMIA/LYMPHOMA (A–C). Bone marrow biopsy and aspirate features of
Burkitt leukemia/lymphoma are illustrated. The bone marrow (or lymph node) will show sheets of highly
proliferating intermediate-sized neoplastic cells with a syncytial appearance. The cells are monotonous but
have a stippled intermediate chromatin pattern with multiple small nucleoli. (C) On the aspirate, the Burkitt
cells have an intermediate size, a denser chromatin than lymphoblasts, and deeply blue cytoplasm with promi-
nent vacuoles.

Thus a brief description of the therapy is warranted in this chapter. Outcomes of Adolescent and Young Adult Patients
Morphologically (Fig. 66.8), the malignant cells are intermediate in TABLE Treated With Pediatric Intensive Regimens: Several
size, have round nuclei with small nucleoli, are intensely basophilic, 66.10 Examples of Recent Trials
and frequently have vacuolated cytoplasms. In a BM biopsy and in
tissue sections, the tumor is classically described as having a “starry ALL-96 DFCI adult ALL C10403 (US
sky” appearance because of the presence of multiple tingible body (PETHEMA) 37 01-175. 38 Intergroup) 39
macrophages with phagocytized cellular debris. Immunopheno- Patient Population
typically, the tumor cells express moderate to strong levels of surface Patients (n) 81 92 318
immunoglobulin M with light chain restriction, indicating origin
of the tumor from a mature B cell. The tumor cells also universally Median age 20 years 28 years 24 years
express the B-cell antigens CD19 and CD20, and germinal center (range) (15–30) (18–50) (17–39)
associated markers such as CD10 and BCL6. Unlike B-ALL, BL cells Gender Male: 62% Male: 61% Male: 61%
do not express CD34 or TdT. The genetic basis of the disease is the Immunophenotype Precursor B Precursor B Precursor B
underlying MYC translocation at band 8q24 to either the Ig heavy and T-ALL and T-ALL and T-ALL
chain region on chromosome 14 or less commonly at the lambda Outcomes
(22q11) or kappa (2p12) loci.
Prompt diagnosis and recognition of this entity is essential because EFS 61% (6 year) 58% (4 year) 66% (2 year)
this is now a highly curable leukemia (in the range of 65% to 80% OS 69% (6 year) 67% (4 year) 78% (2 year)
in recent trials); however, failure to institute appropriate therapy at ALL, Acute lymphoblastic leukemia; EFS, event-free survival; OS, overall
diagnosis for Burkitt lymphoma/leukemia results in emergence of survival.
early resistance and dismal outcomes. Traditional CHOP (cyclophos-
phamide, hydroxydaunomycin, vincristine [Oncovin], and predni-
sone) chemotherapy is inadequate and should not be used. Treatment
should be initiated quickly and consists of aggressive combination
chemotherapy with CNS prophylaxis. These patients are at HR regimens has proven feasible with OS of 91% (3 years) and 79% (2
for the development of tumor lysis syndrome; therefore aggressive years), respectively. Based on these exciting improvements in survival,
hydration and administration of allopurinol and/or rasburicase is the addition of anti-CD20 targeting to frontline therapies for BL is
important. All current regimens rely on short intensive courses of che- now considered the standard of care.
motherapy that incorporate fractionated doses of alkylating agents,
high doses of methotrexate and cytarabine, and intensive intrathecal
prophylaxis. In the United States, commonly used regimens include ADOLESCENTS AND YOUNG ADULTS WITH ACUTE
CODOX-M/IVAC, CALGB 9251, and hyper-CVAD. With these
regimens, approximately 80% achieve CR, and 2-year survival is LYMPHOBLASTIC LEUKEMIA: THE INTERSECTION
around 60% to 70%. In the CALGB 9251 trial, 52% of the patients BETWEEN PEDIATRIC AND ADULT CARE
were alive and in continuous CR at a median follow-up of 5.1
years. Because Burkitt lymphoma/leukemia has a predisposition Evaluation of the outcomes of young adult patients, here defined as
for CNS involvement, aggressive CNS-directed therapy is essential patients between the ages of 15 and 39 years, presents specific chal-
and typically consists of intrathecal administration of methotrexate, lenges. Because of community referral patterns, these patients may
cytarabine, and hydrocortisone. Recurrence after the first 2 years be treated by either pediatric or adult oncologists. As such, the
rarely occurs; therefore maintenance therapy has not been shown to treating physician may view a patient in this age group either as an
be beneficial and is not recommended. older child or as a younger adult. The oncologist will choose a
Because of the strong expression of CD20 in mature B-cell ALL, regimen most appropriate for the population usually seen by that
several groups have incorporated rituximab into the frontline chemo- particular physician. A number of comparisons of the clinical outcome
therapy regimen with impressive further improvements in survival. of adolescents enrolled on adult and pediatric clinical trials (Table
The hyper-CVAD–rituximab regimen was reported in 31 patients 66.10) have resulted in interesting observations about what that
with newly diagnosed Burkitt lymphoma/leukemia with a CR rate appropriate treatment regimen should be and have guided the design
of 86% and a 3-year survival rate of 89%. Similarly, the addition of a number of prospective clinical trials designed specifically for
of rituximab to the treatment in both the GMALL and CALGB AYAs with ALL.