Page 1502 - Hematology_ Basic Principles and Practice ( PDFDrive )

1334 Part VII Hematologic Malignancies

TABLE French Society of Pediatric Oncology Risk Group few hours. The use of uricolytic agents (e.g., urate oxidase, uricase,
84.4 Classification of Mature B-Cell Lymphomas rasburicase) has proven to be superior to allopurinol to reduce the
level of serum uric acid rapidly and improve renal function. Rasbu-
Group Extent of Disease ricase has significantly reduced the need for hemodialysis consequent
Group A Completely resected stage I upon tumor lysis syndrome. Recent protocols incorporate a prophase
Completely resected abdominal stage II of reduced intensity to decrease the risk of severe tumor lysis syn-
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drome. In the setting of abdominal BL, intestinal perforation,
Group B Nonresected stages I and II obstruction, or gastrointestinal bleeding may not occur until after the
Any stage III initiation of chemotherapy as the lymphoma begins to regress.
CNS-negative stage IV with BM involvement 5% to 25%
Localized, resected mature B-cell NHL (including both BL and
Group C CNS-positive stage IV DLBCL) could be cured without significant toxicity by two courses
Stage IV with BM involvement ≥25% (mature B-cell ALL) of chemotherapy. 59,61–63 Advanced-stage BL requires aggressive com-
ALL, Acute lymphoblastic leukemia; BM, bone marrow; CNS, central nervous bination chemotherapy with CNS prophylaxis (Table 84.6). Cyclo-
system. phosphamide, methotrexate, and cytarabine at high doses have been
used most recently, with or without anthracyclines and epipodophyl-
lotoxins. Therapy should be started as quickly as possible upon pre-
sentation because this tumor grows very rapidly, and subsequent
TABLE Berlin-Frankfurt-Münster Risk Group Classification of cycles should be administered in an intensive fashion as soon as
84.5 Mature B-Cell Lymphomas recovery from the last cycle occurs. CNS prophylaxis is needed
Risk Group Resection Status Stage and Initial Serum LDH Level because without it approximately 30% to 50% of patients will relapse
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in the CNS, whereas 6% to 11% develop CNS relapse if adequate
R1 Complete 24
prophylaxis is given. CNS prophylaxis includes high-dose metho-
R2 Incomplete Stages I + II trexate and cytarabine to penetrate the CNS, together with intensive
Stage III and LDH <500 U/L intrathecal chemotherapy. Risk-adapted therapy used in the FAB/
R3 Incomplete Stage III and LDH ≥500 U/L but LMB-96 study and the NHL-BFM95 study conferred an excellent
<1000 U/L EFS in advanced-stage patients. 58–60 Treatment intensity was escalated
Stage IV/B-AL and LDH on the basis of tumor burden and response to therapy. These are the
<1000 U/L and CNS-negative best published outcomes to date, but these regimens have significant
R4 Incomplete Stage III and LDH ≥1000 U/L hematologic toxicity. Researchers in both the FAB/LMB-96 study
Stage IV/B-AL and LDH and the NHL-BFM 95 study successfully reduced therapy for low-
≥1000 U/L and CNS-negative and intermediate-risk patients without a compromise in survival.
However, both studies failed to safely reduce the intensity of therapy
R4 CNS+ Incomplete Stage IV/B-AL and CNS-positive for patients with advanced stages of disease.
B-AL, Burkitt leukemia with ≥25% blasts in the bone marrow; BFM, Berlin- Rituximab is a mouse/human chimeric monoclonal antibody
Frankfurt-Münster; BM, bone marrow; CNS, central nervous system; LDH, against CD20, highly expressed in BL and DLBCL. In adults, the
lactate dehydrogenase.
addition of rituximab to cyclophosphamide, doxorubicin, vincristine,
and prednisone (CHOP) chemotherapy is beneficial for DLBCL and
has been given safely in combination with intensive BL therapy. In
similar to that of classic BL. 55,56 TdT negativity is helpful in distin- children, single-agent rituximab showed activity for BL in a phase II
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guishing BL from B-LBL. window study for newly diagnosed patients, and the COG showed
the safety of adding rituximab to the LMB backbone for the treat-
Prognosis (Staging) ment of BL. 66,67 Current clinical trials address the question whether
The risk group classification developed by the French Society of rituximab added to standard chemotherapy can improve the EFS of
Pediatric Oncology (SFOP) is widely used in current protocols patients with advanced disease.
incorporating risk-adapted therapy (Table 84.4). This system accounts Local radiation therapy has no role in BL, because it is chemo-
for the adverse prognosis associated with CNS or BM involvement sensitive and often diffuse. CNS radiation has been used in the past
and whether localized disease has been resected. Patients with local- for CNS involvement at diagnosis but did not show an impact on
ized or CNS-negative advanced-stage BL have greater than 90% outcome in this group. Surgery is no longer routinely used for BL.
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long-term survival with current therapies. Combined CNS and BM However, patients with localized disease who undergo resection at
involvement and suboptimal response to initial cytoreduction are also diagnosis are eligible for reduced chemotherapy as noted above.
associated with worse prognosis, and poor responders are often strati-
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fied to more intensive chemotherapy in current regimens. High
lactate dehydrogenase (LDH) at diagnosis also carries a worse prog- Diffuse Large B-Cell Lymphoma
nosis and is frequently incorporated in risk classification schemes,
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such as that of the BFM group (Table 84.5). Age greater than 15 DLBCL includes a heterogeneous group of neoplasms of transformed
11
years has a worse outcome for mature B-cell malignancies, but this B cells, accounting for 10% to 13% of pediatric NHL. DLBCL has
may be due primarily to DLBCL rather than to BL. some distinctive biologic and clinical features, described in more
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detail below. DLBCL involving the mediastinum needs to be dis-
Therapy tinguished from primary mediastinal large B-cell lymphoma
Tumor lysis syndrome must be anticipated as a major risk in newly (PMBCL), which represents a distinct subtype of B-NHL in the
diagnosed BL. To help prevent this complication, children at risk WHO classification. In addition, the current version of the WHO
2
should be vigorously hydrated (3–4 L/m /day with D5 1/4 NaCl and classification introduced pediatric follicular lymphoma, marginal
40 mEq/L NaHCO 3; there should be no added potassium) and zone lymphoma, and gray zone lymphoma.
started on allopurinol, a xanthine oxidase inhibitor. The urine pH
should be maintained at about 7.0; at a more alkaline pH, phosphorus Epidemiology
is less soluble, and at a more acidic pH, uric acid is less soluble. In The incidence of DLBCL increases with age, being commoner in the
some cases, mannitol followed by furosemide is required to maintain second decade of life. 14,69 It is rare in children younger than 4 years
urine output. Uricolytic agents (e.g., uricozyme), which has been of age. Although commoner in boys than girls in a 2 : 1 ratio, the sex
used for many years in Europe, directly cleaves the uric acid molecule difference is less than in BL. PMBCL is more common in adolescents,
and results in a precipitous drop in serum uric acid levels within a with no sex difference. 68,70