Fifty years of BMT: risk stratification, donor matching, and stem cell collection for transplantation

In this review, we discuss recipient risk assessment for allo-HCT regarding comorbidities present at baseline to predict non relapse mortality. We further reviewed the incorporation of remission status and cytogenetic risk prior to allograft transplantation to predict relapse rates for hematologic malignancies. HCT-CI and DRI are tools available to physicians to assess the risk–benefit of allo-HCT in patients referred for transplantation. Next, we discuss our algorithm for donor selection and criteria for donor selection in case matched donors are not available. Finally, we discuss our approach for stem cell mobilization, especially in donors failing G-CSF, and our approach for the use of plerixafor and data supporting its use

Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21)

Core-binding factor acute myeloid leukemia with t(8;21) Risk factors and a novel scoring system (I-CBFit)

Background: Although the prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse. Methods: Eleven centers in the US and Europe evaluated 247 patients with t(8;21) (q22;q22). Results: Complete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median diseasefree (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper- or hypodiploidy were included in a scoring system (named I-CBFit). DFS rate at 2 years was 76% for patients with a low-risk I-CBFit score compared with 36% for those with a high-risk I-CBFit score (P <0.0001). Low- vs high-risk OS at 2 years was 89% vs 51% (P <0.0001). Conclusions: I-CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low-risk score)

Central core disease

Central core disease is a congenital myopathy characterized by generalized hypotonia, muscle weakness and presence of central cores on muscle biopsy. It generally presents during infancy. It is familial with autosomal dominant inheritance [Chromosome 19q13.1; Gene Locus RyR1 (Ryanodine receptor gene)]. We report here two cases of central core disease in a 3-year-old male child and 8 year old female child