Pediatric Non-Hodgkin Lymphoma Treatment & Management: Approach Considerations

5/28/2018 Pediatric Non-Hodgkin Lymphoma Treatment & Management: Approach Considerations, Tumor Lysis Syndrome Treatment, Chemot…
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Pediatric Non-Hodgkin
Lymphoma Treatment &
Management
Updated: Feb 06, 2017
Author: J Martin Johnston, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
TREATMENT
Approach Considerations
Proper care of non-Hodgkin lymphoma requires a referral to a comprehensive tertiary care center.
The current intense treatment regimens, particularly those for advanced stages of the disease,
necessitate inpatient administration of chemotherapy, as well as aggressive support by a team
experienced in the care of children with immunosuppression.
Current treatment regimens for lymphoblastic lymphomas (T cell and B cell) are quite similar to
protocols for their leukemic counterparts (T-cell ALL and B-cell ALL). In broad terms, these
therapies are longer and less intensive (particularly with respect to the use of alkylating agents)
than those for small noncleaved-cell lymphoma or LCL, which use relatively high doses of
alkylating agents and antimetabolites.
Current survival rates for patients with advanced disease are 65-75% for T-cell lymphoblastic
lymphomas and 80-90% for those with B-cell lymphomas.
Antibiotics
If present, fever simply may reflect the underlying malignancy. However, consider beginning
empiric, broad-spectrum antibiotic coverage until sepsis or focal infection (eg, due to bowel
perforation) is excluded.
Central venous access
For most patients, a central venous access device is necessary to manage chemotherapy. If
feasible, multiple procedures (eg, line placement, biopsy, lumbar puncture, bone marrow
aspiration) can be performed during one session of anesthesia.
As noted previously, patients with mediastinal disease must be treated cautiously if the use of
general anesthesia is being considered. Unrecognized airway compression can lead to obstruction,
with disastrous consequences.
Rapid progression
Non-Hodgkin lymphomas in children typically grow rapidly, in contrast to the more indolent
lymphomas often observed in adults.
https://emedicine.medscape.com/article/987540-treatment 1/15
To prevent tumoral regrowth and to avoid increasing the short-term risk of complications,
absolutely minimize any delay (eg, to allow healing after an abdominal procedure) between
diagnosis and the start of chemotherapy.
Tumor Lysis Syndrome Treatment

Before and during the initial induction phase of chemotherapy, patients may develop tumor lysis
syndrome, a condition that can result from the rapid destruction of a large number of neoplastic
cells. This destruction causes intracellular ions and metabolic byproducts to be released into the
systemic circulation, which can lead to the rapid development of hyperuricemia, hyperkalemia,
hyperphosphatemia, and hypocalcemia. (Renal involvement by lymphoma is an additional risk
factor.)
Hyperuricemia or tubular obstruction may lead to acute renal failure, requiring dialysis. In general,
this is not a contraindication to continuing chemotherapy. However, some protocols now include a
preliminary phase of relatively gentle cytoreductive chemotherapy designed to avoid these
metabolic complications.
With all patients, administer intravenous fluids at twice the maintenance rates, usually without
potassium. Add sodium bicarbonate to the intravenous fluid to achieve moderate alkalinization of
the urine (pH of approximately 7). This measure enhances the excretion of tumor metabolites. For
example, the solubility of uric acid is 10-12 times higher at a pH of about 7 than it is at a pH of 5,
and the solubility of xanthine is doubled. Avoid a urine pH higher than this to prevent crystallization
of hypoxanthine or calcium phosphate.
Administer allopurinol to prevent or correct hyperuricemia. In high-risk situations (extreme

elevations of lactate dehydrogenase [LDH] and/or uric acid or evidence of impaired renal function
at presentation), consider administration of recombinant urate oxidase (rasburicase [Elitek]). [59]
Follow up the patient's laboratory values to monitor tumor lysis syndrome throughout initial therapy.
Testing may be needed as often as 2-4 times per day. This follow-up is especially important during
the first 48-72 hours of therapy in a patient with bulky disease.
Chemotherapy for Lymphoblastic Lymphoma

The most successful treatment protocols for advanced-stage lymphoblastic lymphoma feature
chemotherapy combinations designed to treat acute lymphoblastic leukemia (ALL).
LSA2L2 protocol
The LSA2 L2 protocol evolved from ALL protocols used at the Memorial Sloan-Kettering Cancer
Center in the early 1960s. The LSA2 L2 protocol features 3 phases of therapy—namely, induction,
consolidation, and repeated cycles of maintenance—given over a total of 2-3 years. [60]
Methotrexate is administered intrathecally for CNS prophylaxis throughout treatment. When this
protocol was first described, it included irradiation of sites of bulky disease; however, radiation is no
longer routinely applied.
Children's Cancer Group protocol 552
Between 1986 and 1989, 143 subjects with lymphoblastic lymphoma (10% with localized disease)
received treatment with a modified LSA2 L2 regimen in a Children's Cancer Group trial (see Table
1, below). Their 5-year event-free survival rate was 74%. [61]
Table 1. Modified LSA2 L2 Therapy in Children's Cancer Group Protocol 552 (Open Table in a new
window)
Phase Drug Route
Cyclophosphamide, vincristine, daunorubicin IV
Induction Ara-C, methotrexate IT
Prednisone PO
Ara-C IV or SC
6-thioguanine PO
Consolidation Methotrexate IT
L-asparaginase IM
BCNU IV
Phase Cycle Drug Route
Maintenance* 6-thioguanine PO
Cyclophosphamide IV
Hydroxyurea PO
Daunorubicin IV
3 Methotrexate PO
BCNU IV
Ara-C IV or SC
Vincristine IV
Source: Children's Cancer Group
Ara-C = cytarabine; BCNU = 1,3-bis(2-chloroethyl)-1-nitrosourea, or carmustine; IM =

intramuscular; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous
* A minimum of 5 repeated courses (total duration of therapy >18 mo) are noted. Each course
of intrathecal methotrexate (day 0 of each course) consists of 4 cycles of rotating drug pairs
that are administered every 2 weeks after blood counts have recovered.
German Berlin, Frankfurt, Muenster treatment protocol
The German Berlin, Frankfurt, Muenster (BFM) protocols have demonstrated excellent results in
patients with ALL or lymphoblastic lymphoma. (See Table 2, below.) [62]
Unlike the LSA2 L2 protocol, the BFM regimen has a reinduction phase. It also features a less
complicated and less intense maintenance phase. In its original report, the BFM protocol included
prophylactic cranial irradiation during reinduction. Patients receiving this treatment had a 6-year
event-free survival rate of 79%.
Table 2. Therapy for Stage III and IV Non–B-Cell Disease* According to BFM Protocol 86 (Open
Table in a new window)
Phases Drug Route
Induction Prednisone, 6-mercaptopurine PO
Vincristine, daunorubicin, cyclophosphamide, Ara-C IV
L-asparaginase IM
Methotrexate IT
6-mercaptopurine PO
Consolidation Methotrexate with leucovorin rescue IV
Methotrexate IT
Dexamethasone, 6-thioguanine PO
Vincristine, doxorubicin, cyclophosphamide, Ara-C IV
Re-induction
L-asparaginase IM
Methotrexate IT
Maintenance† 6-mercaptopurine, methotrexate PO
Source: Berlin-Frankfurt-Munster Group
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous

*Diagnoses included lymphoblastic lymphoma of the T-cell or precursor B-cell type,
immunoblastic T-cell lymphoma, and other peripheral T-cell lymphomas. Of note, patients with
Ki-1+ anaplastic large cell lymphomas (LCLs) were not included.
† Continued until 24 months after diagnosis.
Children's Oncology Group protocols

The most recent Children's Oncology Group phase 3 protocol (A5971) for children with advanced-
stage T-cell lymphoblastic lymphoma featured a 4-way randomization between (1) BFM therapy,
(2) a Children's Cancer Group modified version of BFM therapy (which did not include high-dose
methotrexate/leucovorin during consolidation), and (3) intensified versions of these 2 protocols
(with early introduction of daunomycin and cyclophosphamide). In patients with disseminated

disease, there was no statistical difference in outcomes among the 4 groups, with 5-year event-
free survival of approximately 81%. Age younger than 10 years and imaging response at 2 weeks
were associated with better overall survival. [63]
The Children's Oncology Group is conducting specific protocols to treat T-lymphoblastic lymphoma
and T-cell ALL. In particular, current clinical trials will examine the role of nelarabine (previously
known as compound 506U78), a prodrug of the deoxyguanosine analog 9-beta-D-
arabinofuranosylguanine (Ara-G) that has shown efficacy in T-cell malignancies.
Additional treatment details

For advanced-stage lymphoblastic lymphoma, as for ALL, relatively long intervals of treatment
have been most successful. The maintenance phase typically lasts 18-30 months. Protocols
shorter than this have also been investigated. For example, Children's Cancer Group protocol
5941 examined an aggressive, 11-month, multiagent regimen. In this trial, the 5-year event-free
survival rate was 78% ± 4.5%, and the overall survival rate was 85% ± 3.9%. These results
suggest that the experimental approach is safe and is just as effective as more prolonged
regimens. [64]
When results from several series were combined, patients appeared to have an excellent
prognosis. Long-term survival was approximately 80%.
Despite these findings, a consensus about optimal therapy for lymphoblastic lymphoma is lacking.
Treatment options include the LSA2 L2 protocol and BFM protocol 86 for non-Hodgkin lymphoma
(with the reinduction phase eliminated).
Localized lymphoblastic lymphoma is unusual. In the previously mentioned BFM study, 6 of 77

subjects with non–B-cell non-Hodgkin lymphoma had stage I or II disease. Patients with localized
lymphoblastic lymphoma (n=60) were included in Children's Oncology Group protocol A5971; they
received a Children's Cancer Group modified version of the BFM protocol (as described above)
that included reinduction but had fewer doses of intrathecal chemotherapy during the maintenance
phase. Interestingly, most patients (75%) had a B-precursor phenotype. At a median follow-up of
5.9 years, the 5-year event-free survival rate was 90% (95% confidence interval, 78-96%, with an
overall survival rate of 96% [84-99%]). There were no relapses among the 15 T-cell lymphoblastic
lymphoma subjects. [65]
Regimens simpler than these have demonstrated comparable results. For example, protocol 77-04
from the NCI included alternating cycles of cyclophosphamide, doxorubicin, vincristine, and
prednisone (CHOP) and high-dose methotrexate (with leucovorin as rescue therapy). Aggressive
intrathecal prophylaxis with cytarabine and methotrexate was included; local radiation therapy was
not offered routinely. The total duration of therapy was 15 cycles (approximately 60 wk).
Chemotherapy for Small Noncleaved Cell Lymphoma

Since the mid-1980s, survival rates for patients with Burkitt or Burkittlike lymphomas have
increased dramatically. In general terms, the following lessons have been learned:
Long-term maintenance chemotherapy appears to have no role; therefore, chemotherapy can

be short, with the typical duration being 2-6 cycles, each lasting 3-4 weeks (however, the
intensity of treatment is high for most patients, and inpatient treatment is required)
When observed, relapses occur early, either during therapy or within 6-12 months of its
completion; salvage rates for patients with relapse have been disappointing
Even patients with widely disseminated disease (eg, bone marrow involvement) have a long-
term survival rate of 90%
Involvement of the CNS at diagnosis continues to be an adverse prognostic indicator
Treatment protocol from a Cooperative Group trial

Three cooperative groups conducted an international trial for patients with small noncleaved cell
lymphoma (SNCCL); specifically, the French Society of Pediatric Oncology (SFOP), in France,
Belgium, and the Netherlands; the Children's Cancer Group, in the United States, Canada, and
Australia; and the United Kingdom Children's Cancer Study Group (UKCCSG), in the United
Kingdom and Ireland.
Chemotherapy was based on the SFOP LMB-89 study, in which event-free survival rates ranged
from 100% in group A to 87.5% in group C. Patients with B-cell acute lymphoblastic leukemia
(ALL) were included in this protocol. Subjects were staged (as described above) and then were
assigned to clinical risk groups. (See Tables 3, 4, 5, and 6, below.)
Table 3. Clinical Risk Groups in the International Trial for Patients With SNCCL (Children's Cancer
Group study 5961) (Open Table in a new window)
Subjects,
Clinical
Definition
Group Estimated
%
A 10 All resected stage I or abdominal stage II tumors
Unresected stage I or II tumor, stage III, tumor, or stage IV tumor

B 65
with no CNS involvement and < 25% marrow blasts
C 25 CNS involvement or >25% marrow blasts
Table 4. Standard Therapy in the International Trial for Patients With SNCCL, Group A* (Open
Drug Route
Prednisone PO
Vincristine, cyclophosphamide, doxorubicin IV
Filgrastim (G-CSF), to enhance neutrophil recovery SC or IV

G-CSF = granulocyte colony-stimulating factor; IV = intravenous; PO = oral; SC =

subcutaneous
* See Table 3 for the definition of group A. All subjects received 2 cycles.
With median follow-up of more than 4 years, the 4-year event-free survival rate for group A patients
was 98.3%, and the overall survival rate was 99.2%. [66]
In this trial, patients with advanced disease (groups B and C) received an initial moderately
intensive "reduction" phase of chemotherapy. This was intended to reduce the tumor burden with
minimal risk of inducing or exacerbating tumor lysis syndrome. Patients in group B were
randomized to 1 of 4 treatment arms: the 3 experimental treatment arms involved incremental
decreases in the intensity and/or duration of chemotherapy.
For patients in group B with an "early response" to therapy (at least 20% tumor decrease after 7
days of treatment), outcomes with standard therapy were not superior to outcomes with any of the
experimental (reduced therapy) arms. (See Table 5, below.)
The results indicated, therefore, that pediatric patients with intermediate-risk B non-Hodgkin
lymphoma who have an early response and achieve a complete remission after the first
consolidation course can be effectively treated using a 4-course regimen with a total dose of only
3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin. [67]
Table 5. Standard Therapy in the International Trial for Patients With SNCCL, Group B* (Open
Phase Drug Route
Reduction Prednisone PO
Vincristine, cyclophosphamide IV
Methotrexate/hydrocortisone IT
Phase Cycles Drug Route
Induction 2, starting 7 days Prednisone PO

after reduction
Vincristine, methotrexate with leucovorin IV

rescue, cyclophosphamide, doxorubicin
SC or
Filgrastim (G-CSF)
IV
Methotrexate with leucovorin rescue, Ara-C
Methotrexate/hydrocortisone, Ara-
Consolidation 2
C/hydrocortisone
Filgrastim (G-CSF)
Prednisone PO
Vincristine, methotrexate with leucovorin

Maintenance** 1 IV
Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV =

intravenous; PO = oral, SC = subcutaneous
* See Table 3 for the definition of group B.
** Based on published results from this trial, equivalent outcomes are expected with a reduced
(50%) dose of cyclophosphamide in induction phase 2 and/or elimination of maintenance phase 1.
Group C patients in remission after 3 cycles were randomized to standard versus reduced-intensity
therapy (omitting the last 3 cycles of maintenance). The 4-year event-free survival rate after
randomization was 90% ± 3.1% versus 80% ± 4.2%, respectively, whereas the overall survival rate
was 93% ± 2.7% versus 83% ± 4%, respectively. Patients with either combined marrow and CNS
disease at diagnosis or a poor response to reduction therapy had significantly inferior event-free
survival and overall survival. [68]
Therefore, decreasing therapy in this subgroup of patients appears unwise; standard-intensity

therapy is recommended for children with high-risk B non-Hodgkin lymphoma. (See Table 6,
below.)
Table 6. Standard Therapy in the International Trial for Patients With SNCCL, Group C* (Open
Phase Drug Route
Prednisone PO
Reduction Vincristine, cyclophosphamide IV
Methotrexate/Ara-C/hydrocortisone IT
Prednisone PO
Vincristine, high-dose methotrexate with leucovorin

IV
Induction, cycle 1 starting 7
days after reduction
SC or
Filgrastim (G-CSF)
IV
Induction, cycle 2 Prednisone PO

IV
Filgrastim (G-CSF) SC or
IV
High-dose Ara-C, etoposide (VP-16) IV
SC or
Filgrastim (G-CSF), days 7-21
IV
Consolidation, 2 cycles†
High-dose methotrexate with leucovorin rescue IV
Prednisone PO

Maintenance 1 IV
Maintenance 2 Ara-C, etoposide (VP-16) IT
Prednisone PO
Maintenance 3
Vincristine, cyclophosphamide, doxorubicin IV
Maintenance 4 Ara-C, etoposide (VP-16) IV
Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV =

intravenous; PO = oral, SC = subcutaneous
* See Table 3 for the definition of group C.
† For patients with CNS involvement, during consolidation cycle 1 only.

An alternative treatment approach has been developed over a series of randomized trials by the
German Berlin, Frankfurt, Muenster (BFM) group. [69] In particular, the role of intermediate-dose or
high-dose methotrexate has been investigated among the different clinical risk groups.
Pilot protocols for patients with B-cell non-Hodgkin lymphoma include monoclonal antibodies (eg,
anti-CD20 rituximab) for children with high-risk disease (ie, patients with CNS disease at diagnosis
or those with advanced-stage disease and elevated levels of lactate dehydrogenase).
Chemotherapy for Large Cell Lymphoma

B cell ̶ derived LCLs
Patients with B cell ̶ derived large cell lymphomas (LCLs) are treated effectively using regimens for
SNCCL. [70, 71, 72] Outcomes are similar between the groups.
An alternative therapy is the APO regimen, consisting of doxorubicin (Adriamycin), prednisone, and
vincristine [Oncovin]. [73] Methotrexate and 6-mercaptopurine have been added to this regimen.
A randomized study of children with LCLs (including B-cell LCLs) showed no advantage when
cyclophosphamide was added to the APO regimen. [74] Therefore, this therapy has the advantage
of avoiding exposure to an alkylating agent. However, the cumulative dose of doxorubicin is 450
mg/m2.
Anaplastic (T cell ̶ derived) LCLs
The therapy for anaplastic (T-cell) LCLs is somewhat controversial. Good results (event-free
survival rates of 65-80%) have been reported with a number of protocols. Some were based on
acute lymphoblastic leukemia (ALL) therapy, whereas others were similar or identical to those used
to treat B-cell lymphomas.
The Berlin, Frankfurt, Muenster (BFM) group reported what may be the best results with treatment
for Ki-1+ anaplastic LCLs. [75] The group administered a regimen for B-cell lymphomas that did not
include local radiation therapy. Among 62 patients (none with bone marrow disease and 1 with
CNS involvement), 4 did not achieve remission, 1 died from infection, and 7 had a relapse. At the
time of the report, 50 patients remained in a continuous first episode of complete remission, and 56
were alive. The calculated event-free survival rate at 9 years was 83%.
Subsequent modifications have yielded the ALCL99 protocol as shown below and have further
demonstrated that: (1) dosing methotrexate at 3 g/m2 over 4 hours appears to be at least as
effective (and less toxic) when compared with a dose of 1 g/m2 over 24 hours with the addition of
"triple" intrathecal chemotherapy and (2) the addition of vinblastine (both during chemotherapy and
continuing weekly until 1 year from diagnosis) delayed but did not ultimately prevent relapses. [76,
77]
Table 7. Prephase Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol (Open
Drug Route
Dexamethasone PO
Cyclophosphamide IV
Methotrexate/Ara-C/prednisolone IT
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral.
Table 8. Subsequent Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol
(alternating cycles, repeated 3times each) (Open Table in a new window)
Cycle Drug Route
Dexamethasone PO
Methotrexate with leucovorin rescue, ifosfamide, etoposide (VP-16), Ara-C IV
Dexamethasone PO
B Methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin IV
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral.
Good results have been observed with the relatively uncomplicated APO regimen. In addition, a
randomized study of children with LCL (including B-cell LCL and anaplastic LCL) showed no
apparent advantage when intermediate-dose methotrexate and high-dose cytarabine were added
to an APO backbone. [78]
A report from the SFOP described surprising efficacy for monotherapy with vinblastine for relapsing
anaplastic LCL, even in patients who previously underwent myeloablative therapy with autologous
bone marrow transplantation. [79]
The role of vinblastine in front-line therapy for anaplastic LCL was examined in a Children's
Oncology Group protocol (A5941), which compared the standard APO regimen with an
experimental therapy that included vinblastine. Myelosuppression was more significant than
anticipated and the trial closed early; results have not been published.
The current Children's Oncology Group Phase 2 protocol for anaplastic LCLs uses the ALCL99
regimen (shown above) as a "backbone" and adds (in a randomized fashion) either brentuximab
vedotin, an anti-CD30 monoclonal antibody, or crizotinib, a specific small-molecule inhibitor of the
ALK pathway. [80]
Radiation Therapy
In general, radiation therapy has a limited role in the treatment of pediatric non-Hodgkin lymphoma,
and it is applied almost exclusively in situations deemed to be real or potential emergencies.
Mediastinal irradiation may be helpful in patients with impending airway obstruction, especially if
the use of general anesthesia is being contemplated for biopsy or central line placement.
For patients with lymphoblastic lymphoma, low-dose radiation therapy is often used to treat
neurologic involvement (eg, cranial nerve palsies, intracerebral extension of tumor, paraplegia).
Irradiation has minimal efficacy in patients with SNCCL, presumably because of the rapid growth of
these cells. Although a dose of radiation may result in significant cell kill, rapid regrowth of
surviving cells between doses largely negates the benefit. Hyperfractionated radiotherapy (ie, >1
dose daily) offers a theoretic advantage, as does low-dose continuous irradiation. However, the
unfeasibility of the latter all but precludes its use. [81]
Finally, consider radiotherapy in any patient with documented residual disease after chemotherapy
and in patients with bulky disease at the time of relapse.
Treatment of Relapsed Disease

As front-line therapies for pediatric non-Hodgkin lymphoma continue to evolve and improve,
treatment of relapses is becoming increasingly problematic.
Reinduction regimens use novel chemotherapy combinations, such as ifosfamide, carboplatin, and
etoposide (ICE). Depending on the presence of certain cell-surface markers, monoclonal
antibodies (eg, the anti-CD20 antibody rituximab) may be added to the regimen. [82, 83]
In most cases, myeloablative chemotherapy with either autologous stem-cell rescue or allogeneic
bone marrow transplantation may offer the best option for curative consolidative therapy.
Lymph Node Excision and Dissection

Even for patients with bulky non-Hodgkin lymphoma, debulking surgery is not crucial to effective
therapy. For example, chemotherapy is effective in relieving partial airway or bowel obstruction. In
rare instances, resection may be required for this purpose.
The chief role for surgery is obtaining tissue for diagnosis. Excision of an easily accessible lymph
node (when present) is preferable to a thoracotomy or laparotomy, unless symptoms dictate
otherwise. Even moderately aggressive surgery generally is not necessary or helpful.
One exception, and a potential therapeutic dilemma, involves abdominal B-cell non-Hodgkin
lymphoma. The patient can be assigned to clinical group A (see Table 3) if the following conditions
are met:
An intestinal primary lesion can be resected along with all involved adjacent lymph nodes
The marginal lymph nodes are free of disease
The patient has no evidence of further dissemination (eg, to the CNS or marrow)
In this situation, the prescribed chemotherapy regimen is far less toxic than it would be otherwise.
Therefore, a surgeon treating a reasonably small abdominal non-Hodgkin lymphoma is advised to
perform lymph node dissection and to try to excise all visible areas of tumor.
However, this surgery is performed only if it can be accomplished without causing clinically
significant morbidity. Heroic attempts at resection are best avoided because unresected disease
can still be cured in most patients. Furthermore, prolonged postoperative recovery may delay the
start of chemotherapy and potentially compromise its effectiveness.
Second-look surgery may be helpful for assessing the viability of residual masses, although
second-look procedures require highly individualized approaches. As an alternative, uptake of67
Ga or radiolabeled FDG suggests viability of residual masses in patients whose tumors are gallium
or FDG avid.
Consultations
Intensive care specialist
Patients with pediatric non-Hodgkin lymphoma frequently present in a tenuous condition because
of airway compromise, metabolic derangements, and/or infection. In the initial stages of therapy,
the patient's condition may be unstable or deteriorating. Therefore, the support of a pediatric
intensive care unit is highly desirable.
If available, a pediatric intensivist should be made aware of the patient in the event that respiratory
management or pressor support becomes necessary.
Radiation oncologist
Consider consultation with a radiation oncologist. As previously discussed, however, radiation

therapy generally has a limited role in the treatment of pediatric non-Hodgkin lymphoma, and it is
applied almost exclusively in situations deemed to be real or potential emergencies.
Nephrologist
Notify a nephrologist if the patient has substantial tumor lysis syndrome and if dialysis is under
consideration.
Long-Term Monitoring
A study of a cohort of 200 childhood non-Hodgkin lymphoma survivors found that common late
outcomes in adulthood included obesity (35%), hypertension (9%), and impairment of executive
function (13%), attention (9%), and memory (4%). The study also found a prevalence of impaired
strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%) in the cohort. [84]
Medication

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Pediatric Non-Hodgkin Lymphoma Treatment & Management: Approach Considerations

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5/28/2018 Pediatric Non-Hodgkin Lymphoma Treatment & Management: Approach Considerations, Tumor Lysis Syndrome Treatment, Chemot…

This site is intended for healthcare professionals

Central venous access

Tumor Lysis Syndrome Treatment

Administer allopurinol to prevent or correct hyperuricemia. In high-risk situations (extreme

Chemotherapy for Lymphoblastic Lymphoma

Children's Cancer Group protocol 552

Phase Drug Route

Cyclophosphamide, vincristine, daunorubicin IV

Induction Ara-C, methotrexate IT

Phase Cycle Drug Route

Source: Children's Cancer Group

Ara-C = cytarabine; BCNU = 1,3-bis(2-chloroethyl)-1-nitrosourea, or carmustine; IM =

German Berlin, Frankfurt, Muenster treatment protocol

Phases Drug Route

Induction Prednisone, 6-mercaptopurine PO

Vincristine, daunorubicin, cyclophosphamide, Ara-C IV

Consolidation Methotrexate with leucovorin rescue IV

Vincristine, doxorubicin, cyclophosphamide, Ara-C IV

Maintenance† 6-mercaptopurine, methotrexate PO

Source: Berlin-Frankfurt-Munster Group

Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous

Children's Oncology Group protocols

(with early introduction of daunomycin and cyclophosphamide). In patients with disseminated

Additional treatment details

Localized lymphoblastic lymphoma is unusual. In the previously mentioned BFM study, 6 of 77

Chemotherapy for Small Noncleaved Cell Lymphoma

Long-term maintenance chemotherapy appears to have no role; therefore, chemotherapy can

Involvement of the CNS at diagnosis continues to be an adverse prognostic indicator

Treatment protocol from a Cooperative Group trial

A 10 All resected stage I or abdominal stage II tumors

Unresected stage I or II tumor, stage III, tumor, or stage IV tumor

C 25 CNS involvement or >25% marrow blasts

Vincristine, cyclophosphamide, doxorubicin IV

Filgrastim (G-CSF), to enhance neutrophil recovery SC or IV

G-CSF = granulocyte colony-stimulating factor; IV = intravenous; PO = oral; SC =

Phase Drug Route

Phase Cycles Drug Route

Induction 2, starting 7 days Prednisone PO

Vincristine, methotrexate with leucovorin IV

rescue, cyclophosphamide, doxorubicin

Methotrexate with leucovorin rescue, Ara-C

Vincristine, methotrexate with leucovorin

Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV =

* See Table 3 for the definition of group B.

Therefore, decreasing therapy in this subgroup of patients appears unwise; standard-intensity

Phase Drug Route

Reduction Vincristine, cyclophosphamide IV

Vincristine, high-dose methotrexate with leucovorin

Induction, cycle 2 Prednisone PO

Vincristine, high-dose methotrexate with leucovorin

High-dose Ara-C, etoposide (VP-16) IV

High-dose methotrexate with leucovorin rescue IV

Vincristine, high-dose methotrexate with leucovorin

Maintenance 2 Ara-C, etoposide (VP-16) IT

Vincristine, cyclophosphamide, doxorubicin IV

Maintenance 4 Ara-C, etoposide (VP-16) IV

Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV =

* See Table 3 for the definition of group C.

† For patients with CNS involvement, during consolidation cycle 1 only.

Chemotherapy for Large Cell Lymphoma

Anaplastic (T cell ̶ derived) LCLs