14 research outputs found
Prolonged complete hematologic response in relapsed/refractory T-large granular lymphocyte leukemia after bendamustine treatment
T-large granular lymphocyte
leukemia (T-LGLL) is a chronic clonal proliferation
of effector memory cytotoxic CD3+CD57+CD56- T
cells and the current guidelines suggest
immunosuppressive therapy as first-line therapy, but
the treatment of refractory/relapsed patients is still
challenging due to the lack of prospective studies.
We describe a series of two refractory/relapsed
T-LGLL patients successfully treated with
bendamustine, a chemotherapeutic agent largely used
for B-cell neoplasms, but poorly investigated for the
treatment of T-cell diseases. Complete remission
(CR) was achieved in 3 and 6 months, respectively,
and maintained for at least 20 months. One patient
relapsed after a 20-month CR, but she was
responsive to bendamustine therapy again, obtaining
a further prolonged CR.
Bendamustine as single agent or in combination
could be a feasible therapeutic option in
refractory/relapsed T-LGLL, especially for elderly
patients because of its safety profile
In vitro apoptotic effects of farnesyltransferase blockade in acute myeloid leukemia cells
Farnesyltransferase inhibitors (FTIs)
are a class of oral anti-cancer drugs currently tested
in phase I-II clinical trials for treatment of
hematological malignancies. The in vitro effects of
various FTIs (alpha-hydroxyfarnesylphosphonic
acid, manumycin-A and SCH66336) were tested on
CD34+ KG1a cell line and in primary acute myeloid
leukemia (AML) cells from 64 patients. By cell
viability and clonogeneic methylcellulose assays,
FTIs showed a significant inhibitory activity in
CD34+ KG1a and primary bone marrow (BM)
leukemic cells from 56% of AML patients. FTIs also
induced activation of caspase-3 and Fas-independent
apoptosis, confirmed by the finding that inhibition of
caspase-8 was not associated with the rescue of FTItreated cells. We concluded that other cellular events
induced by FTIs may trigger activation of caspase-3
and subsequent apoptosis, but the expression of
proapoptotic molecules, as Bcl-2 and Bcl-XL, and
antiapoptotic, as Bcl-X(s), were not modified by
FTIs. By contrast, expression of inducible nitric
oxide synthase (iNOS) was increased in FTI-treated
AML cells. Our results suggest a very complex
mechanism of action of FTIs that require more
studies for a better clinical use of the drugs alone or
in combination in the treatment of hematological
malignancies
Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients
SARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production
Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) is a rare hematologic disease, primarily affecting adults or children with immunodeficiency disease. First-line therapy consists of long course of steroids administration, with an early complete response rate (CRr) of 75-80%, but up to 20-30% of patients requires a second-line therapy. Rituximab is the first choice in refractory old AIHA patients, because of its safety and efficacy (early CRr at 80-90% and at 68% at 2-3 years). For this reason, splenectomy is even less chosen as second-line therapy in elderly, even though laparoscopic technique decreased complication and mortality rates. However, splenectomy can be still considered a good therapeutic option with a CRr of 81% at 35.6 months in patients older than 60 year-old, when rituximab administration cannot be performed
Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia.
Autoimmune hemolytic anemia (AIHA) is a rare hematologic disease, primarily affecting adults or children with immunodeficiency disease. First-line therapy consists of long course of steroids administration, with an early complete response rate (CRr) of 75-80%, but up to 20-30% of patients requires a second-line therapy. Rituximab is the first choice in refractory old AIHA patients, because of its safety and efficacy (early CRr at 80-90% and at 68% at 2-3 years). For this reason, splenectomy is even less chosen as second-line therapy in elderly, even though laparoscopic technique decreased complication and mortality rates. However, splenectomy can be still considered a good therapeutic option with a CRr of 81% at 35.6 months in patients older than 60 year-old, when rituximab administration cannot be performed
Persistent decreased bone marrow CD3+CD56+ T lymphocytes are inversely associated with mature granulocytes in myelodysplastic syndromes
Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells
Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic-(allo-) and autologous-(auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto-and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto-and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitarythyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo-or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT
Primary hepatic lymphoma in a patient with previous rectal adenocarcinoma: a case report and discussion of etiopathogenesis and diagnostic tools
Primary hepatic lymphoma is an extremely rare malignancy accounting for 0.016% of all cases of non-Hodgkin lymphomas. Approximately 1-4% of histologies described show a follicular pattern. We report a case of primary hepatic non-Hodgkin lymphoma that developed in a middle-aged woman 3Â years after radical treatment (neoadjuvant chemoradiotherapy and surgery) for a rectal adenocarcinoma. Abdomen ultrasound showed a single nodule in the liver, which raised the issue of differential diagnosis with a metastasis from rectal cancer. After surgical removal of the nodule, histology revealed a primary B cell, stage IE follicular non-Hodgkin lymphoma, confined to the liver; indeed, no foci of lymphoma were found elsewhere in the body
Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells
Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT