24 research outputs found
Highly Elevated Serum Hepcidin in Patients with Acute Myeloid Leukemia prior to and after Allogeneic Hematopoietic Cell Transplantation: Does This Protect from Excessive Parenchymal Iron Loading?
Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre- and post-HCT was present in all patients. Median hepcidin pre- and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P<.0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P<.0005), pre- and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P=.001) and hepcidin (P=.001). No correlation of pre- or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre- and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT
Case Report: Allogeneic Stem Cell Transplantation Following Induction With CPX-351 in Patients With Acute Myeloid Leukemia Is Feasible
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and
treatment-related acutemyeloid leukemia (tAML) after chemotherapy or radiation therapy
for other neoplasms are associated with poor outcomes. CPX-351, a dual-drug liposomal
encapsulation of daunorubicin and cytarabine, has been shown to improve outcomes
in AML-MRC and tAML compared with standard 7+3 regimens. Here we report the
cases of four consecutive patients with AML-MRC or tAML who received CPX-351
as outpatient induction therapy immediately followed by allogeneic hematopoietic stem
cell transplantation (allo-HSCT). Two patients received allo-HSCT in remission (one in
complete remission and one in partial remission) and two patients received allo-HSCT
in aplasia (one at 11 days and one at 52 days after the start of induction therapy with
CPX-351). With a median follow-up of 188 days after allo-HSCT, all but one patient are
alive and two are in remission. Further studies will help define and expand the role of
CPX-351 in the treatment of AML-MRC and tAML, especially in patients expected to
undergo allo-HSCT
Highly Elevated Serum Hepcidin in Patients with Acute Myeloid Leukemia prior to and after Allogeneic Hematopoietic Cell Transplantation: Does This Protect from Excessive Parenchymal Iron Loading?
Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre-and post-HCT was present in all patients. Median hepcidin pre-and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P < .0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P < .0005), pre-and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P = .001) and hepcidin (P = .001). No correlation of pre-or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre-and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT
Salvage Therapy With Polatuzumab Vedotin, Bendamustine, and Rituximab Prior to Allogeneic Hematopoietic Transplantation in Patients With Aggressive Lymphomas Relapsing After Therapy With Chimeric Antigen Receptor T-Cells—Report on Two Cases
Up to 60% of patients with aggressive B-cell lymphoma who receive chimeric antigen
receptor (CAR) T-cell therapy experience treatment failure and subsequently have a poor
prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a
potentially curative approach for patients in this situation. Induction of a deep response
prior to alloHSCT is crucial for long-term outcomes, but the optimal bridging strategy
following relapse after CAR T-cell therapy has not yet been established. Polatuzumab
vedotin, an antibody drug conjugate targeting CD79b, is a novel treatment option for use in
combination with rituximab and bendamustine (Pola-BR) in relapsed or refractory disease.
Patients: We report two heavily pretreated patients with primary refractory diffuse large Bcell
lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) respectively
who relapsed after therapy with CAR T-cells with both nodal and extranodal
manifestations of the disease. After application of three courses of Pola-BR both
patients achieved a complete metabolic remission. Both patients underwent alloHSCT
from a human leukocyte antigen (HLA)-mismatched donor following conditioning with
busulfan and fludarabine and are disease free 362 days and 195 days after alloHSCT
respectively. We conclude that Pola-BR can be an effective bridging therapy before
alloHSCT of patients relapsing after CAR T-cell therapy. Further studies will be necessary
to define the depth and durability of remission of this salvage regimen before alloHSCT
Mobilization of Allogeneic Peripheral Blood Stem Cells in Family Donors with Single-Dose Pegfilgrastim.
Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)
Abstract The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available.</p
Case Report: Allogeneic Stem Cell Transplantation Following Induction With CPX-351 in Patients With Acute Myeloid Leukemia Is Feasible
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and
treatment-related acutemyeloid leukemia (tAML) after chemotherapy or radiation therapy
for other neoplasms are associated with poor outcomes. CPX-351, a dual-drug liposomal
encapsulation of daunorubicin and cytarabine, has been shown to improve outcomes
in AML-MRC and tAML compared with standard 7+3 regimens. Here we report the
cases of four consecutive patients with AML-MRC or tAML who received CPX-351
as outpatient induction therapy immediately followed by allogeneic hematopoietic stem
cell transplantation (allo-HSCT). Two patients received allo-HSCT in remission (one in
complete remission and one in partial remission) and two patients received allo-HSCT
in aplasia (one at 11 days and one at 52 days after the start of induction therapy with
CPX-351). With a median follow-up of 188 days after allo-HSCT, all but one patient are
alive and two are in remission. Further studies will help define and expand the role of
CPX-351 in the treatment of AML-MRC and tAML, especially in patients expected to
undergo allo-HSCT