The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML ...expert panel, consisting of both transplant and nontransplant experts, was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by the American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate- and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed.
Immunoproliferative small intestinal disease (IPSID) is an uncommon disease with a higher prevalence in the developing world. IPSID diagnosis relies mainly on a tissue biopsy and a high index of ...suspicion. Treatment options are variable; however, they mainly include anthracycline-based chemotherapy with or without antibiotics in advanced stages. Because of the paucity of IPSID, our perception of the disease remains narrow, and investigating the optimal lines of therapy and prevention without a complete comprehension of the disease is challenging. In our review, we explore the expansion of knowledge about IPSID, which has been developing over the years, to help increase the detection of IPISD cases and further research the most appropriate lines of therapy and prevention.
Pediatric-inspired non-transplant regimens for adolescent and adult ALL patients are becoming standard in many institutions. We aimed to compare a cohort of patients receiving a pediatric-inspired ...protocol to a cohort of patients treated with adult type ALL therapy followed by allografting after achieving CR1.
Eighty-five adolescent and adult ALL patients treated with CALGB 19802 protocol who received MSD transplant in CR1 were retrospectively compared to a matched cohort of 72 adolescent and adult ALL patients treated with a modified version of Children's Cancer Group (CCG) 1900 protocol.
The five years OS in the allo-HCT cohort was 63.1% compared to 80.2% in the pediatric-inspired chemotherapy arm (P = 0.03). The five years EFS in the allo-HCT arm was 58.8% compared to 61.6% in the pediatric-inspired chemotherapy arm (P = 0.07). The five years DFS in the allo-HCT arm was 58.8% as compared to 71.9% in the pediatric-inspired chemotherapy arm (P = 0.07). The relapse rate in the allo-HCT cohort was 30.58% compared to 21.68% in the pediatric-inspired chemotherapy arm (P = 0.16). The NRM in the allo-HCT cohort was 10.59 as compared to 6.45 in the pediatric-inspired chemotherapy arm (P = 0.3).
For adolescent and adult patients with Ph-negative ALL, pediatric-inspired chemotherapy resulted in higher OS compared to allo-HCT.
Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely ...used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking.
Evaluate the real-world experience of the VCD regimen.
Retrospective.
Tumor registry database of tertiary cancer care center.
newly diagnosed MM patients who received VCD induction and underwent autologous stem cell transplant (ASCT) from July 2007 to July 2020.
response evaluation, progression-free survival (PFS) and overall survival (OS).
87 patients.
Of 102 patients who started induction with VCd, 87 patients experienced a partial response or more overall response rate of 85%). The median age of these 87 patients at diagnosis was 52 years, of which 29.9% presented with renal impairment and 60.3% of patients had stage 2 by the Revised International Staging System (R-ISS). Patients with a standard cytogenetic risk achieved a better response compared to those with a poor cytogenetic risk (
=.044). The post-induction response rates were 6.9% stringent complete remission (sCR), 35% complete remission (CR); 41.4% very good partial response (VGPR), and 16.1% partial response (PR), respectively; the response rates became greater for sCR and CR post-transplantation at day 100 with 16.1% sCR, 35.6% CR, 32.2% VGPR and 16.1% PR, respectively. The median PFS was 49 months and 5 years OS was 84%. PFS was better in patients who achieved sCR vs PR (83 vs 35 months,
=.037). High LDH, high-risk cytogenetic and stage 3 R-ISS showed a worse median PFS and OS.
VCD induction in newly diagnosed MM is highly effective, convenient, tolerable and affordable regimen, especially in low and middle-income countries with limited resources, also with favorable outcomes and survival. while those who did not respond successfully shifted to VRD or VTD.
The usual limitations of a retrospective analysis using registry-level data, no data on quality of life.
Priming donors with G-CSF before BM harvest is reported to improve engraftment and GvHD in recipients. These effects are highly desirable when transplanting patients with non-neoplastic hematologic ...diseases, particularly AA patients. Here we retrospectively report the outcomes of 39 AA patients receiving a primed BM graft from MSD to 43 patients receiving a steady-state BM graft from MSD, otherwise transplanted using a uniform transplant platform. The graft had higher TNC and CD34 cell concentrations in the primed group (
p
< 0.001), and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group (
p
= 0.004 and 0.03, respectively). The OS for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients,
p
-value = 0.01. The cumulative incidence of death without GF was 2.6% in the primed group and 16.3% in the steady-state group,
p
-value = 0.03. There was no difference in GvHD incidence between the two groups. We confirm that priming improved the TNC and CD34 graft concentration and cell dose; this evidence along with other reported studies constitute reasonable evidence to prove that BM priming improve engraftment. We observed no increase in GvHD using primed BM graft.
Central nervous system (CNS) involvement by mantle cell lymphoma (MCL) is rare and portends a poor prognosis. We describe the first patient to have a complete response with front‐line treatment with ...single‐agent acalabrutinib for MCL CNS.
OUTCOME OF APLASTIC ANEMIA ACCORDING TO DISEASE SEVERITY Haroon, Alfadil; Ahmed, Syed Osman Ahmed; Alzahrani, Hazzaa ...
Hematology, Transfusion and Cell Therapy,
October 2023, 2023-10-00, 2023-10-01, Volume:
45
Journal Article
Acute myeloid leukemia (AML) is a hematological malignancy that remains a therapeutic challenge due to the high incidence of disease relapse. To better understand resistance mechanisms and identify ...novel therapies, robust preclinical models mimicking the bone marrow (BM) microenvironment are needed. This study aimed to achieve an automated fabrication process of a three-dimensional (3D) AML disease model that recapitulates the 3D spatial structure of the BM microenvironment and applies to drug screening and investigational studies. To build this model, we investigated a unique class of tetramer peptides with an innate ability to self-assemble into stable hydrogel. An automated robotic bioprinting process was established to fabricate a 3D BM (niche-like) multicellular AML disease model comprised of leukemia cells and the BM's stromal and endothelial cellular fractions. In addition, monoculture and dual-culture models were also fabricated. Leukemia cell compatibility, functionalities (in vitro and in vivo), and drug assessment studies using our model were performed. In addition, RNAseq and gene expression analysis using TaqMan arrays were also performed on 3D cultured stromal cells and primary leukemia cells. The selected peptide hydrogel formed a highly porous network of nanofibers with mechanical properties similar to the BM extracellular matrix. The robotic bioprinter and the novel quadruple coaxial nozzle enabled the automated fabrication of a 3D BM niche-like AML disease model with controlled deposition of multiple cell types into the model. This model supported the viability and growth of primary leukemic, endothelial, and stromal cells and recapitulated cell-cell and cell-ECM interactions. In addition, AML cells in our model possessed quiescent characteristics with improved chemoresistance attributes, resembling more the native conditions as indicated by our in vivo results. Moreover, the whole transcriptome data demonstrated the effect of 3D culture on enhancing BM niche cell characteristics. We identified molecular pathways upregulated in AML cells in our 3D model that might contribute to AML drug resistance and disease relapse. Our results demonstrate the importance of developing 3D biomimicry models that closely recapitulate the in vivo conditions to gain deeper insights into drug resistance mechanisms and novel therapy development. These models can also improve personalized medicine by testing patient-specific treatments.
Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy‐related AML. Large registry‐based data identified sAML as an independent ...poor‐outcome type of AML post allogeneic hematopoietic cell transplantation (allo‐HCT). In our study, we tried to define factors affecting
outcomes of sAML post allo‐HCT, and identify patients with sAML who may truly benefit from allo‐HCT. We retrospectively analyzed the data of 64 patients aged (14‐61 years) with sAML who received allo‐HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor‐risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease‐free survival (DFS; P‐value = .009, and .004, respectively). The cumulative incidence of chronic graft‐versus‐host disease (cGVHD) was significantly lower in sAML patients with poor‐risk cytogenetics (P‐value = .003) resulting in a high risk of death without cGVHD in this group of patients (P‐value = .02). Besides, GVHD relapse‐free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II‐IV cGVHD in the first 2 years post allo‐HCT. We conclude that sAML patients with poor‐risk cytogenetics have a significantly lower DFS post allo‐HCT with a high risk of death without active cGVHD.
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