Feasibility of evidence-based treatment of childhood acute myeloid leukemia in a Sub-Sahara Africa center.

Abstract

e22508 Background: The proportion of Acute Myeloid Leukemia (AML) among childhood leukemias is putatively higher in Sub-Sahara Africa (SSA) compared to Western experiences. However, the treatment of childhood AML is challenging in SSA settings because of inadequate facilities for supportive care to deliver intensive AML regimens and, hence, high treatment-related mortality (TRM). Many pediatric oncology centers in SSA treat childhood AML with a palliative intent, with or without chemotherapy. At the Mulago National Referral Hospital (MNRH)/Global HOPE Center in Uganda, we treat AML with a curative intent. We distinguish Acute Promyelocytic Leukemia (APL) and AML with Down Syndrome (AML-DS) from other subtypes of AML. We treat APL with Children’s Oncology Group (COG) AAML1331 and AML-DS and other AML with modified reduced intensity regimens. We hereby share our experience of anti-cancer and supportive treatment, TRM, remission rates, and short-term overall survival (OS). Methods: We performed a retrospective cohort analysis of children diagnosed with AML between March 2019 and February 2020. The diagnosis of AML was established by bone marrow or peripheral blood morphology and immunophenotyping by flow cytometry according to WHO criteria. All cases of APL were confirmed by cytogenetics for t(15;17). Children without DS or APL received 2 cycles of Cytarabine 100mg/m2 12 hourly Days 1-10, Daunorubicin 50mg/m2 Days 1,3,5 and a single triple intrathecal chemotherapy for induction and 2 cycles of high dose Cytarabine 3000mg/m2 for consolidation. Supportive care comprised warm saline oral rinses, antiseptic baths, antimicrobial prophylaxis with cotrimoxazole, ciprofloxacin and itraconazole, and blood product support. Results: Of the 74 children diagnosed with leukemia 23 (31%) were AML; 4/23 (17%) of AML were APL and 3/23 (13%) were AML-DS. The mean age at diagnosis of AML was 6.1 (SD 4.3) years and 16/23 (70%) were males. For the 4 cases of APL, TRM 1/4 (25%) due to differentiation syndrome, remission rate 2/4 (50%), 1-year OS 75%; 95% CI 32.5-100. For the 3 cases of AML-DS, TRM 1/3 due to severe sepsis with respiratory failure, remission rate 1/3, and 1 was referred to another treatment center. For the other AML, TRM 2/16 (12.5%) due to severe sepsis, remission rate 9/16 (56%) and 1-year OS 78.6%; 95% CI 57.1-100. Conclusions: It is feasible to treat, manage TRM, and achieve remission in childhood AML in the SSA setting. Although there were several TRMs, a remission rate of 56% in the non-APL non-AML-DS is a promising outcome.

Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya

“…However, our CR rate was similar to that in Tanzania 26 . Other literature from sub‐Saharan Africa is lacking, except for one abstract from Uganda that reported a CR rate of 56% with quite a similar induction regimen 37 . Their supportive care included additionally ciprofloxacin prophylaxis and anti‐infective measures like mouth and skin wash 37 .…”

“… 26 Other literature from sub‐Saharan Africa is lacking, except for one abstract from Uganda that reported a CR rate of 56% with quite a similar induction regimen. 37 Their supportive care included additionally ciprofloxacin prophylaxis and anti‐infective measures like mouth and skin wash. 37 This may imply that an extended supportive care regimen can result in a higher CR rate, as a result of less ED's.…”

Treatment outcomes of pediatric acute myeloid leukemia in Western Kenya before and after the implementation of the SIOP PODC treatment guideline

“…From sub‐Saharan Africa, aside from Kenya, only one Tanzanian study is available, wherein all children with AML died within one year after diagnosis 12 . Additionally, one Ugandan abstract on childhood AML reported a CR rate of 56% (9/16), with quite a similar induction therapy and supportive care regimen as in period 2 of our study 14 …”

“…12 Additionally, one Ugandan abstract on childhood AML reported a CR rate of 56% (9/16), with quite a similar induction therapy and supportive care regimen as in period 2 of our study. 14 This study also contributes to the evidence on the implementation of the SIOP PODC pediatric AML-specific adapted treatment guideline 6 and may serve as a valuable example for other LMICs. To validate the proposed expert-opinion based recommendations, this guideline needs to be implemented in LMICs and subsequently evaluated.…”

“…In high‐income countries (HICs), long‐term probabilities of overall survival (pOS) of children with AML currently exceed 70% 7–10 . Considerably poorer rates have been reported in LMICs, 11 in particular in sub‐Saharan Africa 12–14 . Together with low salvage rates after relapse, high rates of treatment abandonment, early death (ED), and treatment‐related mortality (TRM) mainly explain these inferior outcomes in LMICs 11 .…”