Early intervention with allogeneic hematopoietic cell transplantation during chemotherapy-induced aplasia in patients with high-risk acute myeloid leukemia

Abstract

result of the deletions resulting from these rearrangements, clonal B cells or plasma cells will have unique patterns of deletion in the V H yD H yJ H region of the IgH loci. At later stages of B-cell development, IgH switch recombination can reposition the V H D H J H sequence near downstream constant regions (C H ). As a result, clonal B cells or plasma cells that have undergone IgH switch recombination also will have clonal patterns of deletion in the C H region of the IgH locus. Often the B-cell specific deletions described above are large enough to be detected as a homozygous copy number loss using comparative genomic hybridization or single-nucleotide polymorphism arrays. Therefore, copy number changes in the IgH locus have the potential to provide a measure of contamination of clonal B or plasma cells with other cells.Recently, Lopez-Corral et al.2 reported increasing DNA copy number changes detectable in samples from patients with premalignant monoclonal gammopathy of undetermined significance (MGUS) to smoldering multiple myeloma (SMM) to multiple myeloma (MM). As shown in Figure 1a, the inability to detect homozygous, or near-homozygous, deletions within the D H -J H -C H region indicates that substantially more germline D H -J H -C H was detected in the MGUS than in SMM or MM samples they analyzed, indicative of the presence of contaminating DNA from non-tumor cells. This indicates that the purity estimate of their CD138-selected cells (SMM and MM 495%, and MGUS 490%) is inaccurate, particularly for MGUS samples. The extent of this contaminating DNA correlates with the inability to detect whole-genome changes in many MGUS samples (Figure 1b). Therefore, their detection of increasing genomic changes between MGUS, SMM and MM likely relates more to the increasing purity of the samples than to underlying genetic differences between these diseases.Isolation of tumor cells from bone marrow aspirates of patients with MM can achieve a purity of 90-95% by bead selection of cells expressing CD138. However, as the fraction of tumor cells from bone marrow aspirates of patients with MGUS can be 1-2 logs lower than for MM, substantial contamination of purified MGUS tumor cells with non-tumor cells is a significant problem that needs to be rigorously addressed when analyzing purified tumor cells.

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

“…[1][2][3][4][5][6][7] Traditionally, allogeneic HCT was performed using myeloablative conditioning regimens that incorporated high doses of TBI plus chemotherapy or a combination of BU and CY, among other options. 1,2,8,9 The resulting toxicity and consequent morbidity and mortality from the procedure, which exceeded 30% in most cases, limited the applicability of allo-HCT to patients of more advanced age or with a suboptimal performance status or a high HCT comorbidity index.…”

Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial

“…Promising long-term results for allogeneic HSCT in aplasia have been published by our group and others. [26][27][28][29][30] Published leukemia-free survival rates for the FLAMSA-RIC regimen in combination with donor lymphocyte infusion range up to 54% at 4 years from HSCT for a small cohort of 18 patients with complex karyotype AML transplanted as part of first-line therapy. 28 Buchholz et al 24 incorporated clofarabine in a similar approach in 27 patients with adverse karyotype or r/r AML and reported excellent results, translating into relapse-free survival at 2 years of 52% from HSCT.…”

Low platelet count reduces subsequent complete remission rate despite marrow with <5% blasts after AML induction therapy

“…However, the lower CR rate in these patients and the likelihood that patients in CR have fewer infections and receive fewer transfusions than patients not in CR suggest that the < 30,000 platelet group is one in which relatively high risk subsequent therapy such HCT might be considered rather than continued observation. Although none of our 15 patients in the < 30,000 platelet group who failed to enter CR on course 1 received HCT as initial salvage therapy, the feasibility of HCT immediately after failure to obtain CR with initial induction therapy despite < 5% marrow blasts has been demonstrated (4). Other alternatives to the usual practice of continued observation include a 2 nd 3+7 (5) or an investigational agent.…”

“…Xueyan Chen 1 , Laura F. Newell 2 , Hu Xie 3 , Roland B. Walter 3,4,5 , John M. Pagel 3,5 , Vicky K. Sandhu 3 , Pamela S. Becker 3,4,5 , Paul C. Hendrie 4 , Janis L. Abkowitz 4 , Frederick R. Appelbaum 3,5 , Elihu H. Estey 3,4,5 …”