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2.
Int Immunopharmacol ; 101(Pt A): 108292, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1487772

ABSTRACT

Leukopenia is a common manifestation of many diseases, including global outbreak SAS-CoV-2 infection. Granulocyte-macrophage colony-stimulating factor (GM -CSF) has been proved to be effective in promoting lymphocyte regeneration, but adverse immunological effects have also emerged. This study aim to investigate the effect of GM -CSF on BCR heavy chain CDR3 repertoire while promoting lymphocyte regeneration. Cyclophosphamide (CTX) and GM -CSF were used to inhibit and stimulate bone marrow hematopoiesis, respectively. High throughput sequencing was applied to detect the characteristics of BCR CDR3 repertoire in controls, CTX group and GM -CSF group. The white blood cells (WBCs) were quickly reduced (P < 0.05) with lymphocytes decreasing causing by CTX, and the WBCs and lymphocytes returned to the level of controls after GM -CSF treatment. The diversity of BCR heavy chain CDR3 repertoire was also significantly decreased in CTX group. Although there is still a big gap from the controls, the diversity was picked up after GM -CSF treatment. The expression of IGHD01-01, IGHD02-14 and IGHJ04-01 with high-frequency usage regularly and significantly changed in three groups, and many genes with low-frequency usage lost in CTX group and did not reappear in GM -CSF group. Moreover, two shared sequences and accounted for the highest proportion in GM -CSF group have been detected in animal model of chronic lymphocytic leukemia. These results revealed that GM -CSF can partially restore changes in the BCR heavy chain CDR3 repertoire while promoting lymphocyte regeneration, but it may also lead to rearrangement, proliferation and activation of abnormal B cells, which can provide a basis for further study on the adverse immunological effects and mechanism of GM -CSF treatment.


Subject(s)
Cyclophosphamide/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Leukopenia/immunology , Lymphocytes/drug effects , Lymphocytes/immunology , Receptors, Antigen, B-Cell/drug effects , Receptors, Antigen, B-Cell/metabolism , Animals , Complementarity Determining Regions/drug effects , Complementarity Determining Regions/genetics , Complementarity Determining Regions/metabolism , Cyclophosphamide/therapeutic use , Female , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Immunoglobulin Heavy Chains/drug effects , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/metabolism , Immunoglobulin Joining Region/drug effects , Immunoglobulin Joining Region/metabolism , Immunoglobulin Variable Region/drug effects , Immunoglobulin Variable Region/metabolism , Leukocytes/drug effects , Leukopenia/chemically induced , Leukopenia/drug therapy , Lymphocytes/metabolism , Mice, Inbred BALB C , Receptors, Antigen, B-Cell/immunology
3.
Transfus Apher Sci ; 60(5): 103197, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1275746

ABSTRACT

High-dose chemotherapy followed by autologous stem cell transplantation is a major component in the treatment of patients with multiple myeloma. As a prerequisite, the successful collection of a sufficient number of viable peripheral blood hematopoietic CD34+ cells is critical. A common standard protocol for mobilization is currently not defined and critically discussed especially in German-speaking Europe. In times of the Covid-19 pandemic, safe and effective strategies have to be chosen to minimize hospitalization times and severe courses. In this single-center retrospective analysis, safety and efficacy of cyclophosphamide plus etoposide (CE) and growth-factor support (n = 33) was compared to cyclophosphamide mono treatment and growth-factor support (n = 49) in 82 patients with multiple myeloma at first diagnosis. CE was superior to cyclophosphamide mono with a significantly higher number of collected CD34+ cells (15.46 × 106 CD34+ cells/kg vs. 9.92 × 106 CD34+ cells/kg), significantly faster engraftment of granulocytes after stem cell transplantation (day 10.5 vs. day 11.6), shorter duration of the inpatient stay (17.47 days vs. 19.16 days) and significantly less transfusions (8.82 % vs. 30.61 % patients receiving transfusions). The safety profile was comparable in both groups and in line with published data. We conclude that CE is a safe and highly effective mobilization protocol in patients with multiple myeloma at first diagnosis and appears to be superior to the commonly used cyclophosphamide mono regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cyclophosphamide/pharmacology , Etoposide/pharmacology , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cells/drug effects , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/methods , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19 , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Humans , Male , Melphalan/administration & dosage , Middle Aged , Multiple Myeloma/blood , Myeloma Proteins/analysis , Pandemics , Retrospective Studies , SARS-CoV-2 , Transplantation, Autologous
5.
Hematology Am Soc Hematol Educ Program ; 2020(1): 319-327, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-1043090

ABSTRACT

Corticosteroids constitute a first-line therapy for adults and children suffering from nonmalignant immune-mediated hematologic diseases. However, high disease relapse rates during the tapering period or upon drug discontinuation result in long-term corticosteroid use that increases the risk of infection. This same concept applies to other immunosuppressive agents, such as antimetabolites, calcineurin inhibitors, and cyclophosphamide. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection. Screening and antimicrobial prophylaxis against tuberculosis, hepatitis B, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia (PJP) might be indicated in patients who are scheduled to be on high-dose corticosteroids for >4 weeks (>30 mg of prednisone-equivalent dose [PEQ]) or in patients chronically treated (≥8 weeks of continuous or intermittent corticosteroid use) with moderate doses (≥15 to <30 mg PEQ). Antimetabolites (azathioprine, mycophenolate) increase the risk of progressive multifocal leukoencephalopathy (PML); however, other opportunistic infections and viral reactivation have also been reported. In case of new onset of neurological symptoms, PML needs to be considered, and an urgent neurology consultation should be obtained. Cyclophosphamide-induced myelosuppression can lead to serious infections related to neutropenia. PJP prophylaxis should be considered with combination therapy of cyclophosphamide and corticosteroids until a PEQ dose ≤ 5 mg/d is reached. Data on infectious risk when cyclosporine is used in patients with nonmalignant hematologic diseases are lacking. Discontinuation of any immunosuppressive agent during an episode of infection is recommended. In all patients, adherence to an age-based immunization schedule is appropriate.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Antimetabolites/adverse effects , Cyclophosphamide/adverse effects , Cyclosporine/adverse effects , Immunosuppressive Agents/adverse effects , Infections/chemically induced , Adrenal Cortex Hormones/therapeutic use , Aged , Antimetabolites/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Female , Hematologic Diseases/drug therapy , Herpes Zoster/chemically induced , Herpes Zoster/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Infection Control , Pneumonia, Pneumocystis/chemically induced , Pneumonia, Pneumocystis/prevention & control , Strongyloidiasis/chemically induced , Strongyloidiasis/prevention & control
6.
Ann Hematol ; 99(11): 2589-2598, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-746148

ABSTRACT

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Boron Compounds/administration & dosage , Glycine/analogs & derivatives , Multiple Myeloma/drug therapy , Peripheral Nervous System Diseases/chemically induced , Adolescent , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Boron Compounds/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Glycine/administration & dosage , Glycine/adverse effects , Humans , Lenalidomide/administration & dosage , Lenalidomide/adverse effects , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Staging , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/physiopathology , Remission Induction , Survival Analysis , Thalidomide/administration & dosage , Thalidomide/adverse effects , Treatment Outcome
7.
Br J Haematol ; 191(3): 386-389, 2020 11.
Article in English | MEDLINE | ID: covidwho-697165

ABSTRACT

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.


Subject(s)
COVID-19/epidemiology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Pandemics , Plasmablastic Lymphoma/drug therapy , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , COVID-19/complications , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Testing , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Febrile Neutropenia/chemically induced , Febrile Neutropenia/prevention & control , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Infection Control/methods , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Rituximab/administration & dosage , Spain/epidemiology , Superinfection/drug therapy , Vincristine/administration & dosage , Vincristine/adverse effects
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