Influence of transplantation regimen on prognostic significance of high-level minimal residual disease before allogeneic stem cell transplantation in children with ALL

Abstract

Summary:High MRD levels before transplantation in children receiving T cell-depleted unrelated grafts for relapsed ALL were associated with a 100% relapse risk. We report on two children with relapsed ALL who underwent non T cell-depleted BMT from unrelated donors. Despite a high residual tumor load pretransplant and the occurrence of only aGVHD grade I, they are still in second complete remission 2.7 and 5.2 years after transplantation, respectively. Thus, we propose that the transplant regimens influence the prognostic significance of high MRD levels pre-BMT. Bone Marrow Transplantation (2001) 28, 1087-1089. Keywords: childhood ALL; bone marrow transplantation; minimal residual disease Minimal residual disease analysis by clone-specific IgH and TCR gene rearrangements is accepted as a reliable method for monitoring submicroscopic disease in childhood ALL. Several studies revealed the highly predictive value of MRD in the early phase of front-line chemotherapy. [1][2][3] Recent emphasis is being placed on the application of MRD before transplantation, since one of the major problems after SCT is the high incidence of relapses even in patients transplanted in morphological remission. Thus, the detection of submicroscopic levels of leukemic cell burden is thought to be of additional prognostic value in outcome prediction after allo-BMT for ALL.Recently, Knechtli et al 4 showed that high MRD levels of equal or more than 10 −3 within 4 weeks before transplantation were significantly correlated with a poor outcome after transplantation. Their study was performed in children with ALL transplanted from T cell-depleted matched and mismatched unrelated grafts in first, second or subsequent remission. We report here on two children who underwent allogeneic BMT for relapsed ALL with non-T cell-depleted grafts from unrelated donors. Both chil- dren had high MRD levels of equal or more than 10 −2 using clonotypic IgH and TCR gene rearrangements as molecular markers 3 weeks before transplantation. They are still in CR after an observation time of 2.7 and 5.2 years from transplantation, respectively. These data suggest that different transplantation regimens may influence outcome after BMT in childhood ALL and, thus, the prognostic value of MRD analysis pre-BMT. PatientsWe retrospectively analyzed MRD levels 2 to 4 weeks before allogeneic non-T cell-depleted BMT in 13 children with ALL. Two of the four patients with high MRD levels of equal or more than 10 −2 pre-BMT did not relapse and are reported here. Both children were treated according to current BFM protocols (ALL-BFM 90; ALL-Rez-BFM 96 protocol). 5 They were in morphological remission before BMT. Bone marrow graft processing and supportive care were done according to standard procedures. HLA compatibility was assessed by conventional serological typing for class I and class II, and by DNA sequencing of class II antigens. Patient 1Pre-B ALL was diagnosed in a female aged 11.3 years. WBC count at diagnosis was 68 × 10 9 /l. Cytogenetic analysis revealed a normal karyoty...

Clinical significance of minimal residual disease in patients with acute leukaemia undergoing haematopoietic stem cell transplantation

“…Minimal residual disease levels prior to HSCT are directly related to risk of relapse post‐HSCT, particularly in ALL (Krejci et al , ; Bader et al , ; Leung et al , ). It should be noted, however, that high levels of MRD pre‐transplant do not completely preclude success (Schneider et al , ; Bader et al , ; Leung et al , ). Moreover, we found that the adverse prognostic impact of any given level of MRD was lower in children with ALL or AML transplanted in recent years (2000–2007) as compared to earlier cohorts (Leung et al , ).…”

Estudio de la enfermedad mínima residual en el cáncer infantil

“…El número de copias del gen CBFb-MYH11, tras la inducción y consolidación, fueron significativamente más altas en los que recayeron comparado con los que mantuvieron remisión completa, lo que confiere a esta determinación de EMR un importante valor predictivo 22,23 . El éxito de los trasplantes de progenitores hematopoyéticos (TPH) en leucemias infantiles, tanto alogéni-cos como autólogos, depende de la persistencia o reaparición de EMR en el paciente trasplantado [31][32][33][34] . Estudios retrospectivos muestran que la presencia de EMR en LAL, analizada previamente a un TPH, se asocia a un alto riesgo de recaída posterior 31 .…”