Advanced Burkitt Lymphoma in Sub-Saharan

original reports Africa Pediatric Units: Results of the Third

Prospective Multicenter Study of the Groupe
Franco-Africain d’Oncologie Pédiatrique
Gabrielle C. Bouda, MD1; Fousseyni Traoré, MD2; Line Couitchere, MD3; Marie-Anne Raquin, MD4; Koffi M. Guedenon, MD5;
Angele Pondy, MD6; Claude Moreira, MD7; Mbola Rakotomahefa, MD8; Mhamed Harif, MD9; and Catherine Patte, MD4
abstract

PURPOSE To evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-
Saharan African pediatric centers.
PATIENTS AND METHODS Children with advanced-stage BL (stages II bulky, III, and IV) treated with the
GFAOP–Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015
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were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2
induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 con-
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

solidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the
dose of 3 g/m2.
RESULTS Four hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease.
Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole
protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment.
Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related
to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110
are known to be in CR with a follow-up . 1 year, indicating a high rate of loss to follow-up. Twelve-month overall
survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and
IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus
57% (P = .0062) beyond 34 days.
CONCLUSION The GFA-LMB2009 protocol improved patients’ survival. Early dose intensity of treatment is
a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.
J Global Oncol. © 2019 by American Society of Clinical Oncology
Licensed under the Creative Commons Attribution 4.0 License

INTRODUCTION from 30% in the 1970s to 90% in the 1990s in de-

veloped countries through consecutive prospective
Burkitt Lymphoma (BL) is the most frequent non-
studies. The identification of clinical and biologic
Hodgkin lymphoma (NHL) in children and accounts
factors and the initial response to treatment have led to
for 50%-60% of childhood NHL. It is endemic in the stratification into therapeutic groups.9-16 An intensive
area known as the Burkitt belt, where it represents pulse polychemotherapy of 1 to 6 months with the
. 50% of childhood cancers in sub-Saharan Africa.1-3 shortest intervals between courses and CNS pro-
BL is characterized by very rapid progression, with phylaxis is essential. Cyclophosphamide, high-dose
Author affiliations
a tendency to early invasion of the CNS and the bone methotrexate (HDMTX) and cytarabine (high dose
and support
information (if marrow (BM). More than two-thirds of the patients are [HD] in advanced diseases) appear as major drugs, to
applicable) appear at diagnosed at advanced stages of the disease.4-8 which are added vincristine, doxorubicin, etoposide,
the end of this
Major advances in the management of childhood and corticosteroids.3,9-17 The improvements in sup-
article.
B-cell NHL were made in recent years thanks to portive care and team experience led to a gradual
Accepted on October
1, 2019 and national and international collaborations. Most of the reduction in toxic death rate from 10% to , 1% in
published at current treatment protocols are derived from the 10 years.9-13 Medium- and long-term cardiac and
ascopubs.org/journal/ Lymphomes Malins B (LMB) protocols designed by the gonadal toxicity and secondary cancer risk decreased
jgo on December 3,
Société Française d’Oncologie Pédiatrique (SFOP) or because of all these adaptations.9,14,16
2019: DOI https://doi.
org/10.1200/JGO.19. the Berlin-Frankfurt-Münster protocols of the German- In developing countries, health infrastructures are
00172 Austrian group. Overall survival (OS) rate increased insufficient and inadequate for cancer care. Access to

1
 Bouda et al

CONTEXT
Key Objective
Advanced stage Burkitt lymphomas need a short (a few months) but intensive polychemotherapy to be cured. The Groupe
Franco-Africain d’Oncologie Pédiatrique developed in 7 sub-Saharan units the GFA-LMB2009, a protocol based on the
Lymphomes Malins B regimen without doxorubicin. High-dose methotrexate, 3 g/m2, was administered with alkaline
hyperhydration and folinic acid rescue 24 hours later, without methotrexate level measurements.
Knowledge Generated
The overall survival was 60% at 1 year (n = 400). Patients with stage III disease who started second induction course within
34 days (n = 123) had overall survival of 76%, versus 57% (P = .0062) for those who started beyond 34 days (n = 124).
This demonstrates the importance of the early dose intensity.
Relevance
This study indicates that, despite many difficulties, a significant percentage of children with Burkitt lymphoma can be cured
in sub-Saharan countries. It is necessary to improve supportive care and to reduce treatment abandonment and loss to
follow-up.
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Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

care for the population remains limited geographically survival of patients with advanced-stage disease, while
and financially, which generates diagnostic delays and taking into account local conditions.
abandonment.18,19 Moreover, human expertise is often
lacking, making the application of reference protocols PATIENTS AND METHODS
difficult. In the Groupe Franco-Africain d’Oncologie
This is a prospective study carried out from April 2009 to
Pédiatrique (GFAOP), two previous studies on the
September 2015. Some units joined during the study.
treatment of BL were carried out,4,5 thanks to the
gained experience and improved patient management of The protocol was reviewed and approved by the GFAOP
these study teams. This third multicenter study, named board. Each unit was committed to present the protocol to
GFAOP–Lymphomes Malins B (GFA-LMB) 2009, was their institution in accordance with ethics standards for
initiated in sub-Saharan units to continue to improve research in the country.

Diagnosis: Stage II bulky, III, and IV

Prephase: 1 or 2 courses
Induction: 2 COPM
Consolidation: 2 CYM

CR No CR

Stage II bulky, III, and IV:

Stage IV: maintenance phase
Stage II bulky and III: intensive chemotherapy
1-4 maintenances
Follow-up 2 COPADM
Follow-up
2 mini CYVE

Relapse Relapse CR Follow-up No CR Palliative

FIG 1. Protocol strategy. COPM, cyclophosphamide, vincristine, prednisone, high-dose methotrexate; COPADM,
addition of doxorubicin (adriamycin) to COPM; CR, complete remission; CYM, cytarabine, high-dose methotrexate;
CYVE, HD cytarabine, vepeside (VP16).

2 © 2019 by American Society of Clinical Oncology

 The Third GFAOP Burkitt Study in Sub-Saharan Africa

TABLE 1. GFA-LMB2009 Treatment Courses

Regimen Dose Administration Days
Prephase
CMP 500 mg/m2 IV 1
MTX + HC 15 mg each IT 1
Repeat course at day 8 if necessary
Induction phase: COPM 1 and 2: started 1 wk after the prephase
VCR 1.5 mg/m2 (max 2 mg) IV 1
CPM 500 mg/m2/d IV (in 2 fractions) 2, 3, 4
HDMTX 3 g/m2 IV in 3-h infusion 1
Folinic acid 15 mg/m2 every 6 h PO or IV (12 doses) 2, 3, 4
Pred 60 mg/m2/day IV or PO 1-7
MTX + HC 15 mg each IT 2, 6
Consolidation phase: CYM 1 and 2
HDMTX 3 g/m2 IV in 3-h infusion 1
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2
Folinic acid 15 mg/m every 6 h PO or IV (12 doses) 2, 3, 4
Ara C 100 mg/m2/day SC (in 2 fractions) 2-6
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

MTX + HC 15 mg each IT 2
Ara-C + HC 30 mg + 15 mg IT 7
Maintenance phase for stage IV: monthly alternating courses
m1
VCR 2 mg/m2 (max 2 mg) IV 1
CPM 500 mg/m2/day IV (in 2 fractions) 2, 3
ADR 60 mg/m2 IV 1 h 2
HDMTX 3 g/m2 IV 4 h 1
2
Folinic acid 15 mg/m every 6 h PO or IV (12 doses) 2, 3, 4
Pred 60 mg/m2/day PO 1-7
MTX + HC + Ara-C 15 mg + 15 mg + 30 mg IT 2
m2 and m4
Ara-C 100 mg/m2/day SC (in 2 fractions) 1-5
VP16 150 mg/m2/day IV 90 min 1, 2, 3
m3
VCR 2 mg/m2 (max 2 mg) IV 1
2
CPM 500 mg/m /day IV (in 2 fractions) 1, 2
ADR 60 mg/m2 IV 1 h 1
2
Pred 60 mg/m /day PO 1-7

NOTE. COPM2, CYM1, and CYM2 were started as soon as possible when absolute neutriphils count . 1,000 or 500 in ascending phase and
platelets were . 100,000 between day 15 and day 21. In case of failure, more intensive chemotherapy was proposed. Dose of each IT drug
must be adapted when age , 3 years.
Abbreviations: ADR, doxorubicin (adriamycin); Ara-C, cytarabine; COPM, cyclophosphamide, vincristine, prednisone, and HDMTX; CPM,
cyclophosphamide; CR, complete remission; max, maximum dose by injection; CYM, cytarabine, HDMTX; HC, hydrocortisone; HDMTX, high-
dose MTX; IT, intrathecal; IV, intravenous; MTX, methotrexate; PO, orally; pred, prednisone; SC, subcutaneously; VCR, vincristine; VP16,
etoposide.

Eligibility decision. In November 2012, patients with stage II bulky

All patients ≤ 18 years old with BL were registered in the disease were also included. Criteria of exclusion were:
database. Children with stage III and IV disease without terminal disease at presentation, HIV positivity, prior che-
CNS involvement and with , 70% blasts in BM were eli- motherapy, intensive or prolonged corticosteroid treatment,
gible for the study. However, some patients with . 70% and socioeconomic conditions considered incompatible
blasts in BM and/or CNS disease were included by medical with the treatment. Families had to pay for their child’s care,

Journal of Global Oncology 3

 Bouda et al

except for drugs sent by GFAOP. Parents had to give consolidation. CR was defined as disappearance of all
consent to participate to the study. tumor masses confirmed at clinical examination, x-ray, and
ultrasound. In patients with initial BM or CNS involvement,
Diagnosis and Staging
examination of BM smear or CSF was performed to confirm
Diagnosis was made by cytology using fine-needle aspi- CR. Patients in clinical CR were considered in CR even with
ration of the tumor or a pathologic fluid (pleural, ascites) a small residual mass stable on imaging. In case of residual
and/or histopathology. Immunohistochemistry was not masses . 5 cm, removal was recommended for histology
available and not performed. Mandatory investigations examination to confirm remission or not.
included clinical examination, abdominal ultrasound and
Statistical Method
chest x-ray, CBC count, BM aspiration, CSF direct anal-
ysis, serum chemistry, and HIV serology. Hepatitis B Data were collected in each unit, recorded, transmitted,
serology was recommended. A computed tomography and centralized in a common database in Gustave Roussy
scan was sometimes performed. Murphy classification for analysis. Overall survival (OS) was defined from the first
was used for staging classification.20 Stage II disease was day of chemotherapy to death or last follow-up and was
also subdivided into nonbulky and bulky, defined as estimated using the Kaplan-Meier method.22 Patients lost to
maxillofacial stage II with the presence of one of the follow-up on progression were considered as dead.
criteria: tumor diameter . 7.5 cm, orbital lesion, . 3 RESULTS
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affected regions, or lactate dehydrogenase greater than

Of the 562 patients registered in the database during the
the twice normal value.
6.5 years of the study, 162 were not eligible: stage
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

Chemotherapy Regimen IV CNS positive or with BM involvement . 70% (25%),

The GFA-LMB2009 protocol was a polychemotherapy bad nutritional status and/or socioeconomic conditions
regimen based on the LMB group B scheme without (20%), prior treatment (17%), death before treatment
doxorubicin in the induction phase (Fig 1, Table 1).12,16 The (15%), refusal (15%), no confirmation of the diagnosis
prephase consisted of 1 or 2 courses of cyclophosphamide (5%), HIV infection (3%). The 400 eligible patients were
and intrathecal injection, at 1-week intervals. In the 2 in- treated in 7 sub-Saharan African centers: 5 in West Africa
duction courses of COPM (cyclophosphamide, vincristine, (Abidjan, n = 71; Bamako, n = 125; Dakar, n = 15; Lomé,
prednisone, HDMTX) and in the 2 consolidation courses n = 15; Ouagadougou, n = 146), 1 in Central Africa
of CYM (cytarabine, HDMTX), HDMTX was administered (Yaoundé, n = 26), and 1 in Madagascar (Antananarivo,
at 3 g/m2 in 3 hours followed by 12 injections of folinic acid n = 2).
rescue starting 24 hours later. There were 2 intrathecal Patient Characteristics
injections per course. A maintenance phase with 1-4
Median age was 7.3 years (8 months to 18 years) with a sex
sequences was planned for stage IV disease. In case of
ratio of 1.9:1 (male:female). Median number of siblings was
failure (partial remission, tumor progression, or stable
4 (0-11). Socioeconomic level was low in 90% and middle
tumor), more intensive chemotherapy was recom-
in 10% of the families. A total of 75% of the fathers and
mended, including doxorubicin (COPM course; in-
85% of the mothers were illiterate. Median distance to
cluding doxorubicin [adriamycin] in COPADM), HD
reach the unit was 185 km (1-3,000 km). The possibility of
cytarabine (CY), and etoposide (vepeside [VE] at reduce
housing near the unit was mentioned by 55% of the
dose [mini-CYVE courses])21 when supportive care could
families.
be ensured.
Diagnosis was based on cytology in 91% of cases, pa-
Supportive Care
thology in 6%, and both in 3%. Tumor sites and stages are
Patients were systematically treated for parasites according presented in Table 2. Diagnosis of NHL without precision
to the local ecosystem by albendazole and/or metronida- was reported for 25% of patients. They were included in the
zole. Recommendation for prevention/treatment of tumor study on the probability of BL because of epidemiology and
lysis syndrome (TLS) was detailed in the protocol using tumor site. BM aspiration was performed in 337 (84%)
alkaline hydration and allopurinol. Nutritional support was patients. Thirty-four patients had CNS involvement, and 8
given, and the infected patients were treated with anti- had Burkitt leukemia with blasts . 70%. They should have
biotics and/ or antifungals according to the case. Trans- been excluded and treated more intensively but were
fusion was recommended when hemoglobin level was treated according to the GFA-LMB2009 protocol; their
, 7 g/dL, or in case of clinical intolerance, and when plate results are presented.
let count was , 20 109/L, or in case of a hemorrhagic
Treatment and Outcome
syndrome.
Of the 400 patients, 231 (58%) patients received the
Response Criteria complete treatment, whereas it was interrupted for 169
Patients were evaluated clinically after each course. (42%; Table 2). A first complete remission (CR1) was
Complete remission (CR) had to be obtained after observed in 195 patients (49%). Thirty-seven (19%)

4 © 2019 by American Society of Clinical Oncology

 The Third GFAOP Burkitt Study in Sub-Saharan Africa

TABLE 2. Initial Tumor Sites, Treatment Completion, and Outcome According to Stage
Stage II Bulky Stage III Stage IV Total
Site, Treatment, or Outcome (n = 26; 7%) (n = 304; 76%) (n = 70; 17%) (N = 400)
Primary sites
Abdomen 121 20 141
Head and neck 26 (9*) 14 40
Abdomen, head and neck 151 35 186
Abdomen and pleural 19 19
Lymph nodes 6 6
Testicular 2 2
Other sites 5 1 6
BM 36 36
CNS 29 29
CNS and bone marrow 5 5
Treatment
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Complete treatment 15 177 39 231 (58%)

Treatment interrupted 11 127 31 169 (42%)
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

CR 15 (1†) 159 (7†) 21 (3†) 195 (49%) (11†)

Treatment abandonment 7 62 21 90 (22%)
Outcome
All death 7‡ 93 25 125
Toxic death during initial treatment 3 37 9 49
Death after progression/relapse 2 55 16 73
Death from unknown cause 2 1 0 3
Alive 19 (2§) 211 45 275
Alive . 1 year 5 (1§) (1†) 105 (17§) (2†) 0 110 (18§) (3†)

NOTE. Data presented as No. unless otherwise indicated.

Abbreviations: BM, bone marrow; CR, complete remission.
*Patients with orbital involvement.
†Patients in second CR.
‡One death after 2-year follow-up of unknown cause.
§Patients in first CR despite treatment abandonment and with no other treatment.

patients relapsed (32 locally and 5 in BM and/or CNS) and The interruption of treatment was linked to abandonment
31 received second-line chemotherapy, with 11 second for 90 patients (22%), change for more intensive treatment
complete remissions (CR2). because of insufficient response for 19, and deaths for 60

TABLE 3. Main Grade 3-4 Adverse Events Among Patients With Stage III Disease During Initial Treatment
Prephase* COPM 32 Courses CYM 32 Courses
Adverse Event (%) (n = 424) (n = 539) (n = 372)
Febrile neutropenia 10 15 4
Documented infection ,2 3 3
GI disorders including mucositis 3 11 5.3
Hb , 7 g/100 ml 6 5 7
RBC transfusion, No. (%) 1† 5 (0.9) 3 (0.8)
Platelet transfusion, No. (%) 3 (0.5) 2 (0.5)
Toxic deaths, No. (%) 6† (1.6) 20 (3.7) 3 (0.8)

NOTE. Deaths (n = 8) after intensification are not in this table.

Abbreviations: COPM, cyclophosphamide, vincristine, prednisone, high-dose methotrexate; CYM, cytarabine, high-dose methotrexate.
*A total of 120 patients had a second cyclophosphamide prephase.
†The patient received a transfusion and died of malaria crisis.

Journal of Global Oncology 5

 Bouda et al

100 100
90 90 logrank, P = .0062

80 80
Overall Survival (%)

Overall Survival (%)

70 70
60 60
50 50
40 40
30 30
20 Stage III 20
Stage II Interval COPM2 < 34 d
10 10
Stage IV Interval COPM2 ≥ 34 d

0 3 6 9 12 15 18 0 6 12 18 24
Time (months) Time (months)
No. at risk: No. at risk:
304 207 156 125 107 99 89 123 75 60 48 31
26 17 9 8 6 5 5 124 68 38 30 22
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70 39 17 9 8 6 5

FIG 3. One-year overall survival of patients with stage III disease according
FIG 2. One-year overall survival of all patients according to stage.
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

to the interval between start of treatment and start of second induction

course (COPM2). Vertical bar denote 95% CI of the of the actuarial rates.
others. Among those who abandoned treatment, 25 pa-
tients (2 stage II, 23 stage III) were and remained in CR, and before versus later than 34 days: 76% versus 56%, re-
7 patients achieved CR with another treatment (6 stage III spectively (Fig 3). For the 116 patients who received
and 1 stage IV). COPM2 after 34 days, the reason for delay . 34 days,
known in 66 of 116 patients (57%), was infection or febrile
A total of 125 (31%) deaths were reported. Initial treatment-
neutropenia in only half of them.
related deaths included 49 patients (12%), occurring
during prephase (9), COPM (29), and CYM (3) courses and DISCUSSION
treatment intensification (8); some deaths occurred while This third study of the GFAOP is the first to our knowledge
the tumor was not controlled. Seventy-three patients (18%) that concerned 7 centers in sub-Saharan Africa and with
died as a result of a tumor and 3 from undetermined such a high number of included patients (400). The 1-year
causes. survival rate of 60% for all the patients is encouraging,
Main treatment-related toxicities of stage III are detailed in knowing that the experience of the teams was not equal in
Table 3. Any grade 3 or 4 toxicity occurred in 35% of terms of seniority and that local realities were not similar,
patients during the prephase, in 37% during induction with very recent structuring of childhood cancer care in
phase, and in 18% during consolidation phase. Only 2 some countries.
cases of TLS are reported; both patients died. During the 3 GFAOP studies, the number of patients treated
One-year OS of all patients was 60% (95% CI, 54% to 66%) in the sub-Saharan units increased, especially that of pa-
and, respectively, 63% (95% CI, 37% to 83%) in patients tients with stage III disease, who represent the majority of
with stage II bulky disease, 60% (95% CI, 53% to 66%) in patients with BL (76% in the current study). In the first GFA
patients with stage III disease, and 31% (95% CI, 16% to study (2001-2004),4 in which most patients were from
52%) in patients with stage IV disease (Fig 2). Among the North African units, 3 sub-Saharan units enrolled 55 pa-
270 patients alive without tumor progression at last eval- tients with stage III disease, whose OS was 44% (95% CI,
uation, only 110 were alive in CR with a follow-up . 1 year, 28% to 62%). In the second GFAOP study (2005-2009),
including 18 who abandoned treatment. exploring the possibility of curing patients with cyclo-
phosphamide monotherapy,23 6 sub-Saharan units par-
We focused on patients with stage III disease, who rep-
ticipated. The 18-month OS of the 128 patients with stage
resented 76% of the population. There was no statistical
III disease was only 30% using cyclophosphamide alone
difference in OS whether patients were treated before or
and 43% (95% CI, 34% to 54%) using the second-line
after April 2012 (P = .3).
treatment.5 In this third study, 304 patients with stage III
For the 247 patients who finished induction treatment, disease from 7 sub-Saharan units were treated, whose
dose intensity was measured by the interval between start survival was 60% (95% CI, 53% to 66%). Parallel to this
of treatment and start of the second induction course increase in participation, it seems that survival improved,
(COPM2). Median interval was 34 days. OS was signifi- although this is difficult to demonstrate. Despite a trend
cantly different (P = .0062) if patients started COPM2 toward better outcome, there was no significant difference

6 © 2019 by American Society of Clinical Oncology

 The Third GFAOP Burkitt Study in Sub-Saharan Africa

in survival between the first and second periods of the Results in patients with stage IV disease were disap-
current study (56% before April 2012 v 68% after; P = .3). pointing, with an OS of 31% and a median follow-up of only
This might be linked to the diverse experiences of the teams 5 months. However, it should be noted that more than half
and the gradual recruitment in the study of new centers not of these patients had CNS involvement (34 of 70) and/or
yet accustomed to the protocol. a massive BM infiltration, which should have excluded
them from the study. But the teams considered that it was
The association of cyclophosphamide, vincristine, pred-
not possible to give more intensive treatment similar to
nisone, and MTX is widely used in childhood B-NHL, al-
those that allowed an increased survival rate for patients
though the dose of each drug, especially MTX, differed
with CNS-positive disease to 75%, while avoiding brain
among the treatment protocols. Generally in the regimen
irradiation.12,14,15,21 In Davidson’s trial,26 survival of patients
called COMP, MTX doses are between 30 mg/m2 and
defined as group C (CNS involvement and BM infiltration
300 mg/m2.24 In this study, GFA-LMB2009, in which
. 25%) increased from 30% with COMP to 66% with LMB
courses are called COPM, MTX was administered at the
group C regimen (HDMTX 8 g/m2, and HDCY + VP16). This
dose of 3 g/m2 to ensure CNS prophylaxis and better
confirms the necessity for more intensive chemotherapy
systemic diffusion. This HD was feasible despite no MTX
and/or other treatment, such as immunotherapy, in higher-
level measurement but required hyperhydration, admin-
risk BL.26,27,34,35
istration of folinic acid rescue, and alkaline urine output
Toxic death, especially during the first month of treatment,
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surveillance by a trained nursing team. The common point

of these protocols is the improvement of survival rates is the main important problem in the management of BL.7
between 50% and 76.5% versus a maximum survival of In the first GFAOP study with a majority of North African
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

50% for monotherapies.4,5,7,8,25-29 units, toxic death rate was 10.5%, with a decrease from
11.5% in the first year to 8% during the third year of the
The recommended interval between start of treatment and
study, and it was 7.8% in the second study, with a less toxic
COPM2 was 25 or 32 days, depending on whether the
regimen.4,5 In the current study, it was 12.25% (49 pa-
patient received one or two prephase courses. In reality, the
tients), with the majority of patients dying during prephase
interval ranged from 29 to 41 days (median, 34 days). A
and induction (38 patients), which is a more toxic regimen
significant difference in survival was observed for patients
performed in less-experienced sub-Saharan units. The
with stage III disease depending on the time of adminis-
majority of patients are admitted with advanced diseases
tration of COPM2: 76% versus 57% when administration
requiring more intensive chemotherapy, and when disease
before or after 34 days (P = .0062; Fig 3). This confirms the
is advanced the risk of toxic death is greater during the first
importance of early dose intensity in the treatment of BL, as phases of treatment.12-14,27 Improvements are possible in
was shown by the SFOP/SFCE studies, in particular in the sub-Saharan units and require training of personnel at all
FAB/LMB96 study.2,16,26,30 For the 43% of patients who levels. This will be obtained through organization of unit
received COPM2 later than 34 days, there was no signifi- meetings with discussion on the causes of death and the
cant complication reported in the previous courses. This way to avoid them. It is also a reason for adaptation of the
suggests that reduction of intervals between courses could treatment according to the local possibilities.19,27,36,37
be improved by better communication between parents
and trained staff, better planning of biologic examinations, Infections and febrile neutropenia were the main adverse
and having a reserve stock of essential drugs. effects during prephase and induction in approximately
15% of cases. Eight patients with stage III disease (2.6%)
Indeed, BL is the most prevalent childhood cancer in sub- received RBC transfusions, and the estimated need was
Saharan Africa.4,5,7,18,31 It should also be recognized that 6% on average during the treatment, indicating a need for
drugs used for BL are among the cheapest antineoplastic improving the supply of blood products. Of note, these
drugs. However, it does not have the same consideration as infection rates and transfusion requirements are much
malaria, tuberculosis, or HIV.19 Initiatives like those of the lower than in regimens including doxorubicin. Poly-
GFAOP, which aim to develop protocols adapted to local chemotherapy is responsible for immunosuppression and
conditions, must be encouraged.7,16,26,27 Concerning total is a source of infections requiring adapted supportive
cost of drugs, for stage III disease the Cameroon2008 care.4-8,12,25-27 Only 2 cases of TLS were reported. It is
protocol7 is 2.5 times cheaper than the GFA-LMB2009 possible that this adverse effect was under-reported, but
protocol: 166 euros versus 417 (purchasing prices by prephase treatment with cyclophosphamide only, associ-
GFAOP in February 2009), with similar OS rates. This must ated with TLS prevention, allowed attenuation of this
be balanced with cyclophosphamide total dose: re- manifestation and its consequences before starting
spectively, 7.2/9 g/m2 (risk 2/3: high probability of infertility) induction.
versus 3.5/4 g/m2 (no risk of infertility).32,33
Treatment abandonment rate was 22% (similar in all
Patients with stage II bulky disease were few (n = 26). Their stages), and loss to follow-was important, since only 110 of
inclusion was recent, and it was difficult to draw any the 275 alive patients have a follow-up . 1 year. These 2
conclusion. problems still constitute major challenges for care in

Journal of Global Oncology 7

 Bouda et al

Africa.18, Among the causes of abandonment, there are not the Pediatric Oncology in Developing Countries Group,
only financial difficulties but also multiple social and cul- which has developed guidelines for the management of
tural reasons that must be taken into account.38 However, BL in resource-limited settings. 36 The collaboration
advances are notable despite the heterogeneity of the started in sub-Saharan Africa opens the way to extend
conditions.8 Cancer management is costly from all aspects. prospective studies and research.19,27 In addition, biologic
Some social and psychological assistance mechanisms to specificities of BL may help to initiate new therapeutic
help parents confronted with this hard reality are in-
strategies.3,39
dispensable. Some reasons for abandonment can be
overcome by a better involvement of all health care pro- This trial shows that despite considerable difficulties in
viders. Greater involvement of politicians and leaders is cancer care, especially in centers more recently opened, it
indispensable for childhood cancer care, especially in drug is possible to cure a significant number of sub-Saharan
distribution. An improvement in pediatric oncology man- children with BL. The GFA-LMB2009 protocol is effective
agement will without doubt benefit all pediatric disease. for patients with stage II bulky and III BL, provided that it is
GFAOP efforts to find effective protocols with reason- applied rigorously, respecting course intervals and with
able costs are in agreement with the recommendations of improvement of supportive care.
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AFFILIATIONS AUTHOR CONTRIBUTIONS

1
CHU Yalgado Ouédraogo, Ouagadougou, Burkina Faso Conception and design: Fousseyni Traoré, Line Couitchere, Mhamed Harif,
Copyright © 2025 American Society of Clinical Oncology. All rights reserved.

2
CHU Gabriel Touré, Bamako, Mali Marie-Anne Raquin, Catherine Patte
3
CHU de Treichville, Abidjan, Côte d’Ivoire Provision of study material or patients: Gabrielle C. Bouda, Fousseyni
4
Gustave Roussy Hospital and GFAOP Database Center, Villejuif, France Traoré, Line Couitchere, Koffi M. Guedenon, Angele Pondy, Claude
5
CHU Sylvanus Olympio, Lomé, Togo Moreira, Mbola Rakotomahefa
6
Centre Mère-Enfant, Fondation Chantal Biya, Yaoundé, Cameroun Collection and assembly of data: Gabrielle C. Bouda, Marie-Anne Raquin,
7
Hôpital Aristide Le Dantec, Dakar, Sénégal Catherine Patte
8
HJRA, Antananarivo, Madagascar Data analysis and interpretation: Gabrielle C. Bouda, Marie-Anne Raquin,
9
Hôpital 20 Août 1953, Casablanca, Morocco Catherine Patte
Manuscript writing: All authors
CORRESPONDING AUTHOR Final approval of manuscript: All authors
Gabrielle C. Bouda, MD, Pediatric Oncology Unit, CHU Yalgado Accountable for all aspects of the work: All authors
Ouédraogo, 09 BP 1545 Ouagadougou 09, Burkina Faso; e-mail:
[email protected].
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by authors of
PRIOR PRESENTATION this manuscript. All relationships are considered compensated unless
Presented in part at the Société Internationale d’Oncologie Pédiatrique otherwise noted. Relationships are self-held unless noted. I = Immediate
(SIOP) annual meeting, Cape Town, South Africa, October 8-11, 2015; Family Member, Inst = My Institution. Relationships may not relate to the
and the SIOP Africa meeting, Marrakech, Morocco, April 5-8, 2017. subject matter of this manuscript. For more information about ASCO’s
conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.
org/jgo/site/misc/authors.html.
SUPPORT
Open Payments is a public database containing information reported by
Supported by Institut Gustave Roussy, Villejuif, France; Ligue Nationale
companies about payments made to US-licensed physicians (Open
Contre le Cancer, France; Société Française des Cancers de l’Enfant;
Payments).
Société Française de Pédiatrie; Société Internationale d’Oncologie
Pédiatrique; Œuvres Hospitalières Françaises de l’Ordre de Malte, Paris, No potential conflicts of interest were reported.
France; Fondation Sanofi-Espoir, Paris, France; Association Pathologie,
Cytologie et Développement, France; and Association Lalla Salma,
Rabat, Morocco. ACKNOWLEDGMENT
We thank B. Mallon for her help with editing this article.

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