Philadelphia-positive B-lymphoblastic leukemia in a middle-income country – A real-world multicenter cohort

Silva, Wellington F; Silvério, Alexandre; Duarte, Bruno; Aguiar, Thais Ferraz; Bendlin, Rodrigo Miguel; Massaut, Ires H. B.; Pagnano, Kátia Bórgia Barbosa; Velloso, Elvira Drp; Rocha, Vanderson; Rego, Eduardo Magalhães

doi:10.1016/j.leukres.2021.106666

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…Even though previous experiences with corticosteroids plus TKI have been published, this study validated this approach, even for young patients. In LMICs, this approach holds particular value as there are more reports of induction-related deaths [12,13].…”

Section: Frontline Induction In Ph+ Allmentioning

confidence: 99%

“…During this initial phase, once again, early identification of the BCR-ABL1 fusion allows more patients to avoid intensive upfront chemotherapy, reducing early mortality [12,39]. It is worth noting that the Philadelphia chromosome is more frequent in older patients; therefore, lower-intensity protocols are often more appropriate for most patients [40].…”

Section: Frontline Induction In Ph+ Allmentioning

confidence: 99%

“…A study by Ravandi et al reported that 31 out of 72 patients considered eligible for the Hyper-CVAD plus dasatinib trial received fewer than the intended 8 cycles due to poor tolerance [59]. Some publications have also noted excessive toxicity during consolidation, which appears to be associated with the choice of chemotherapy prescribed in these block [12,59,60]. High doses of methotrexate (MTX) and cytarabine (HD-AraC) are typically administered, along with anthracyclines, cyclophosphamide, and clofarabine in some protocols.…”

Section: Consolidation and Maintenance Therapymentioning

confidence: 99%

“…These findings suggest that chemotherapy reductions and discontinuations must be undertaken cautiously in Ph+ ALL, especially in fit patients and in resource-constrained scenarios. Protocols that schedule alloSCT immediately after induction, with minimal or no chemotherapy before the procedure, can be challenging in LMICs where transplantation availability is limited [12,61].…”

Section: Consolidation and Maintenance Therapymentioning

confidence: 99%

“…Whereas most researchers at the cutting edge of Ph+ ALL are excited about this outlook, most clinicians worldwide are now challenged by these new approaches. In real life, patients from low-to middle-income countries (LMIC) have limited access to BCR-ABL1 monitoring and newer agents, such as ponatinib and blinatumomab, and might experience increased toxicities with conventional chemotherapy [12][13][14][15]. These agents are difficult to afford for public agencies in LMIC.…”

Section: Introductionmentioning

confidence: 99%

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How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings

Silva,

Rego

2023

Cancers

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Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities. Currently, it is advisable to use less intensive induction regimens for Ph+ ALL. These regimens can achieve high rates of complete remission while causing fewer induction deaths. For consolidation therapy, chemotherapy should remain relatively intensive, with careful monitoring of the BCR-ABL1 molecular transcript and minimal residual disease. AlloSCT may be considered, especially for patients who do not achieve complete molecular remission or have high-risk genetic abnormalities, such as IKZF1-plus. If there is a loss of molecular response, it is essential to screen patients for ABL mutations and, ideally, change the TKI therapy. The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.

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Section: Frontline Induction In Ph+ Allmentioning

confidence: 99%