ALL-REZ BFM - The Consecutive Trials for Children with Relapsed Acute Lymphoblastic Leukemia

Abstract

The BFM studies for relapsed childhood acute lymphoblastic leukemia (ALL) were started in 1983, at a time when cure rates for ALL were still lower and the number of children with ALL relapse equaled about the number of children with newly diagnosed neuroblastoma. Today, relapses have become relatively rare events in ALL although, because of the frequency of ALL, they are still a significant cause of death in children and adolescents. With currently used treatment modalities, cure rates of about 50% after relapse can be achieved, and, together with the improved results of front-line therapy, the survival rate of childhood ALL is now about 90%. Most children with extramedullary and late bone marrow (BM) relapses achieve a second CR; remission rates in patients with high-risk features, however, remain still unsatisfactory. With improved techniques allogeneic hematopoietic stem cell transplant (HSCT) has become a relatively safe treatment but is not necessary for all patients as postremission therapy. HSCT is not required in children with isolated extramedullary and late BM relapses with rapid response to induction therapy measured by molecular techniques (minimal residual disease, MRD) but absolutely indicated in patients with early BM relapses and systemic relapses of T-cell ALL. For patients with insufficient response innovative therapies such as small molecules or targeted immunological or pharmacological approaches are urgently required. Efforts have to be made, therefore, in order to detect potential biological or molecular targets, which can be used for individualized, more effective and hopefully less toxic therapies in the future.

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

“…The findings suggest that the more intensive induction treatment with dexamethasone especially reduced the incidence of less resistant and better salvageable relapses. This was substantiated by a lower rate of prognostically favorable features among the patients who had relapsed in the dexamethasone arm, such as positivity for ETV6-RUNX1, favorable relapse risk group (S1/S2), 16 or favorable treatment response during the first-line therapy (ie, MRD load of , 5 3 10 24 at week 12) (Table 4).…”

“…*Risk groups in relapsed patients with pB-ALL are defined as follows: S1, late (ie, .6 mo after cessation of frontline treatment) isolated extramedullary relapse; S3, early (ie, .18 mo after initial diagnosis and before 6 mo after cessation of frontline treatment) isolated bone marrow relapse; S4, very early (ie, within 18 mo after initial diagnosis) isolated or combined bone marrow relapse; S2, all others. 16 CI, confidence interval; DXM, dexamethasone; MRD, minimal residual disease; NA, not applicable; PDN, prednisone.…”

“…This critical reflection of the different types of events is important when evaluating the quality of treatment, because patients with relapsed ALL have a realistic chance to be rescued by a second-line therapy. 16,29,30 The evaluation is even more complicated if a considerably higher treatment burden in the experimental arm does not result in a significantly higher death rate and is therefore not reflected when calculating event-free survival rates. The AIEOP-BFM ALL 2000 study produced a statistically significant difference in 5-year event-free survival of 3% between the dexamethasone and prednisone arms in the large group of 3720 patients.…”

Targeted therapy of CNS leukemia?

“…Furthermore, while the majority of children with ALL are cured, up to a third of the relapses involve the CNS. 3 Thus, more specific and less toxic drugs are urgently needed for the prevention and treatment of CNS relapse. Leukemic cells typically grow in the cerebrospinal fluid (CSF) in the subarachnoid space (see figure panel A).…”

An Unusual Site of Acute Lymphoblastic Leukaemia Relapse: Challenge for Gynaecologists

“…Secondary involvement of female genitourinary system [1,2] is more common in lymphoma than leukaemia [3,4]. In leukaemia, acute myeloid leukaemia (AML) is known to have extra medullary involvement (chloroma, granulocytic sarcoma, etc.)…”