Outcome of Relapsed Childhood Acute Lymphoblastic Leukemia in Resource-Poor Country : Warrants the Need for Immunotherapy

Introduction:

The overall survival (OS) rate for children with acute lymphoblastic leukemia (ALL) treated at King Hussein Cancer Center is approximately 80%, aligning with published results of the Total XV regimen.

Method:

From December 2003 until August 2023, children/adolescents (<18 years at diagnosis) with ALL in first and subsequent relapses were studied. Treatment of relapse consisted of reinduction regimens followed by intensive continuation therapy and hematopoietic stem cell transplantation (HSCT) in selected patients. The poor prognostic group (PPG) included patients who did not achieve remission after salvage chemotherapy and were referred to palliative care.

Results:

The study included 160 patients with a median age of 5 years (range: 0.4-19.8 years), followed for a median of 71 months (range: 4-248 months). Sites of relapse were: bone marrow (BM) in 64%(N=103) of the patients, combined relapse in 19 %( N=30) and isolated extra-medullary Relapse (IEM) relapse 17%(N=27). Complete remission (CR2) rates for all patients were 64% and vary according to time and site of relapse (100% for IEM, 56% for isolated BM/combined: 90% for late relapses, and 39% for early/very early relapses). The estimated 5-year-EFS and OS for the whole group were 30% and 40 %, respectively. Five-year-OS for patients with BM relapse was 29%, combined relapse 58%, and IEM 66%. Five-year-OS for patients with very early relapse was 12%, early relapse 36%, and late 74%.

Forty patients (39%) continued on chemotherapy after achieving CR2, and sixty-two patients (61%) underwent HSCT, with 60 (59%) alive in continuous complete remission (CCR) at last follow-up. All patients (N=58) in the PPG died of the disease.

In univariable analysis, worse OS was observed in patients <1 or≥10-years at diagnosis, those T-cell-immunophenotype, CNS 3 at diagnosis, BM and very early relapses. In multivariable analysis : age (p=0.02), site of Relapse( p=0.019) and time of relapse(p=0.009) were prognostic.

In univariable analysis, worse EFS was observed in patients <1 or≥10-years at diagnosis, T-cell-immunophenotype, CNS 3 at diagnosis, unfavorable cytogenetic at diagnosis, BM and very early relapses. In multivariable analysis Site of Relapse ( p=0.02)and time of relapse(p<0.001) were prognostic.

Conclusions

At our center, more than one-third of relapsed ALL patients were cured. However, survival rates are low in high-risk relapsed ALL (very early and isolated BM relapses). Conventional chemotherapy and adequate supportive care failed to salvage this high-risk group, indicating the need for immunotherapy as a bridge to allogeneic hematopoietic stem cell transplantation.

No relevant conflicts of interest to declare.