Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter ...randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America.
Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157).
Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS.
Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.
Allogenic hematopoietic cell transplantation (HSCT) is typically the preferred curative therapy for adult patients with acute myeloid leukemia, but its use has been reduced as a consequence of ...limited donor availability in the form of either matched-related donors (MRD) or matched-unrelated donors (MUD). Alternative options such as unrelated umbilical cord blood (UCB) transplantation and haploidentical HSCT have been increasingly studied in the past few decades to overcome these obstacles. A human leukocyte antigen- (HLA-) haploidentical donor is a recipient’s relative who shares an exact haplotype with the recipient but is mismatched for HLA genes on the unshared haplotype. These dissimilarities pose several challenges to the outcomes of the patient receiving such a type of HSCT, including higher rates of bidirectional alloreactivity and graft failure. In the past 5 years, however, several nonrandomized studies have shown promising results in terms of graft success and decreased rates of alloreactivity, in part due to newer grafting techniques and graft-versus-host disease (GVHD) prophylaxis. We present here a summary and review of the latest results of these studies as well as a brief discussion on the advantages and challenges of haploidentical HSCT.
aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between ...MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with
aberrations. We observed no significant differences between MDS and AML regarding
genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus
variant allele frequency (VAF) > 50%. In multivariate analysis, unadjusted Cox models revealed the following variables as independent risk factors for mortality: AML (vs. MDS) (hazard ratio HR: 2.50, confidence interval CI: 1.4-4.4,
= 0.001), complex karyotype (HR: 3.00, CI: 1.4-6.1,
= 0.003), multihit status (HR: 2.30, CI 1.3-4.2,
= 0.005), and absence of hematopoietic cell transplant (HCT) (HR: 3.90, CI: 1.8-8.9,
= 0.0009). Clonal dynamic modeling showed a significant reduction in
VAF with front-line hypomethylating agents. These findings clarify the impact of specific covariates on outcomes of
-aberrant myeloid neoplasms, irrespective of the diagnosis of MDS versus AML, and may influence HCT decisions.
Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma patients and is associated with significant improvement in progression-free survival (PFS), ...complete remission rates (CR), and overall survival (OS). However, majority of patients eventually relapse, with a median PFS of around 36 months. Relapses are harder to treat and prognosis declines with each relapse. Achieving and maintaining “best response” to initial therapy is the ultimate goal of first-line treatment and sustained CR is a powerful surrogate for extended survival especially in high-risk multiple myeloma. ASCT is often followed by consolidation/maintenance phase to deepen and/or maintain the response achieved by induction and ASCT. Novel agents like thalidomide, lenalidomide, and bortezomib have been used as single agents or in combination. Thalidomide use has been associated with a meaningful improvement in PFS and EFS, however, with substantial side effects. Data with lenalidomide maintenance after-ASCT is favorable, but the optimal duration of lenalidomide maintenance is still unclear. Bortezomib use has been associated with superior outcomes, predominantly in high-risk myeloma patients. Combination regimens utilizing a proteasome inhibitor (i.e., bortezomib) with an immunomodulatory drug (thalidomide or lenalidomide) have provided the best outcomes. This review article serves as a review of the best available evidence in post-ASCT approaches in multiple myeloma.
INTRODUCTION Allogeneic stem cell transplant (Allo-SCT) is a powerful tool in the treatment of acute myeloid leukemia (AML) and offers the only potential chance of cure. In the context of residual ...disease testing for leukemia, it allows detection of dominant and subclonal mutations both at diagnosis and in posttreatment monitoring and has the ability to detect molecular aberrations suspicious for persistent leukemia at low levels and across the gamut of subtypes. Prior studies have suggested that mutations in genes involved in modification of the epigenome - either through DNA methylation regulation or histone modification - tend to be permissive of AML transformation but not sufficient in and of them to give rise to leukemia. TABLE 1 Patient characteristics Findings in diagnostic specimen Findings in pretransplant specimen Case Age Sex Karyotype Blast count (%) Mutations Median mutation percentage Blast count (%) Mutations IDATE mutation only Median mutation percentage Relapse free survival in months Overall survival in months Pretransplant marrow containing at least one non-IDATE mutation 1 66 M inv(3) - 14 NRAS, NPM1 33 10 NRAS N 8 2.1 + 2.1 2 57 F 46, XX 83 NPM1, DNMT3A, IDH2, PTPN11 46 40 NPM1, DNMT3A, IDH2 N 43 6.1+ 6.1 3 67 M 46, XY 34 NPM1, PTPN11 39 8 NPM1 N 3 1.3+ 1.3 4 81 M '-7, +r(7), 94 JAK2, IDH2, RUNX1, EZH2, FLT3-TK, PTPN11 56 30 JAK2, IDH2, RUNX1, EZH2, FLT3-TK, RUNX1 N 27 6 months 9.4 5 64 M 46, XY 83 NPM1, IDH1, SRSF2, NRAS, PTPN11 42 5 NPM1, IDH1, NRAS, IDH2 N 29 4.0+ 4 6 77 M 46, XY 80 NPM1, DNMT3A, SF3B1, SETBP1, TET2, NRAS, KRAS, PTPN11 47 <5 FLT3-ITD, NPM1 N 1 0.4 + 0.4 7 43 M inv(9) 92 FLT3-ITD, NPM1 DNMT3A IDH2 46 0 NPM1, DNMT3A, IDH2 N 0 2.6 9.5 8 73 M 46, XY 97 FLT3-ITD, NPM1, DNMT3A 45 0 FLT3-ITD, NPM1, DNMT3A N 4 3.0 + 3 9 36 F t(6;9) (p23;24) 20 FLT3-ITD, NRAS 24 3 FLT3-ITD N 12+ 12 Pretransplant marrow showing IDATE only mutations 10 68 M 46, XY 62 ASXL1, DNMT3A, IDH1 21 6 ASXL1, DNMT3A, IDH1 Y 44 62.2+ 62.2+ 11 35 M 46, XY 97 NRAS, DNMT3A, IDH1, BCOR, STAG2 48 0 DNMT3A, IDH1 Y 5 12.4 23.3+ 12 56 F NP 74 FLT3-ITD, NPM1, DNMT3A 58 0 DNMT3A Y 1 36.8+ 36.8+ 13 77 M 46, XY NA FLT3-ITD, NPM1, TET2 33 0 TET2 Y 24 2.6+ 2.6 14 80 F 46, XX 67 FLT3-ITD, DNMT3A, RUNX1, IDH2 45 <5 DNMT3A Y 40 54.9+ 54.9+ Pretransplant marrow showing no mutations 15 59 M 46, XY 25 NPM1, NRAS, IDH2 42 2 None – 0 56.2+ 56.2+ 16 44 F 46, XX 76 FLT3-ITD, RUNX1, WT1 46 <5 None – 0 23.4 26.5 17 27 F 46, XX NP NPM1 40 1 None – 0 55+ 55+ Abbreviations: N, no; NP, not performed; Y, yes; +, censored (lost to follow-up for OS; lost to follow-up or death without relapse for RFS).
Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe ...infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.
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