Immunosuppressive effects of pentostatin.

Kraut, Eric H.; Neff, Jane; Bouroncle, Bertha A.; Gochnour, Diane; Grever, Michael R.

doi:10.1200/jco.1990.8.5.848

Cited by 93 publications

(33 citation statements)

References 16 publications

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“…56,57 The use of CI pentostatin in this regimen was well tolerated, with minimal mucositis, gastrointestinal side effects, or evidence of tissue damage that may have had a impact on the development of serious aGVHD. 53,55 Since the present regimen was not associated with end organrelated toxicities even in patients with pre-existing hepatic and renal insufficiency, cytokine release from damaged tissue was minimized. Alternative conditioning regimens incorporating either antithymocyte globulin or anti-CD2 antibodies along with CSA have also been successful in attenuating aGVHD.…”

Section: Survival and Disease Responsementioning

confidence: 99%

“…Pentostatin induces prolonged T-cell depletion and in experimental models has been shown to prevent or decrease the severity of aGVHD when administered prior to the infusion of allogeneic HSCs. 54,55 In a murine allogeneic transplant model, mice receiving a regimen containing pentostatin showed a decrease in the clinical and histologic signs of aGVHD and cGVHD. 54 While pentostatin induces a prolonged depletion of circulating T cells, the long-term effects on host immunoregulatory T cells are not known.…”

Section: Survival and Disease Responsementioning

confidence: 99%

See 1 more Smart Citation

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

Miller

Roberts

Chan

et al. 2004

Bone Marrow Transplant

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Summary:In all, 55 patients at high risk or ineligible for a conventional allogeneic hematopoietic stem cell transplant (HSCT) received a regimen consisting of extracorporeal photopheresis, pentostatin, and reduced dose total body irradiation. The median age was 49 years (18-70 years); 44 received a sibling and 11 an unrelated HSCT; 44% were over the age of 50 years and 31% had undergone a prior HSCT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Full donor chimerism was documented in 98% by day þ 100. The 1000-day nonrelapse mortality was 11%. The median follow-up is 502 days (154-1104 days). The 1-and 2-year overall survival (OS) and event-free survival (EFS) are 67, 58 and 55%, and 47%, respectively. Patients who had not received a prior HSCT or had less than three prior chemotherapy regimens had a 71% OS and 67% EFS at 1 year. Greater than grade II aGVHD developed in 9% and chronic GVHD (cGVHD) in 43%, and extensive in 12% and limited in 31%. Of the patients, 86% who engrafted had a disease response, 72% had complete and 14% partial responses. This novel reduced intensity preparative regimen was well tolerated and associated with a low incidence of transplant-related mortality and serious acute and cGVHD. pentostatin Current allogeneic hematopoietic stem cell transplant (HSCT) preparative regimens are designed to administer the maximally tolerated doses of chemotherapy and/or radiation therapy in an attempt to eradicate residual disease, ablate host hematopoiesis, and immune suppress the recipient to ensure engraftment of donor hematopoietic stem cells (HSC). While this approach is curative for many patients, it is also associated with 30-50% transplantrelated mortality (TRM) in patients over the age of 50 years. 1 While advances in supportive care and the management of acute graft-versus-host disease (aGVHD) have decreased the TRM and morbidity associated with an allogeneic HSCT, its application remains limited to patients who are able to tolerate the side effects of high-dose chemotherapy administered as part of a conventional preparative regimen. 2 Recent studies suggest that disease control and engraftment of allogeneic HSCT can be achieved following nonablative doses of chemoradiotherapy. [3][4][5] Moreover, in various diseases, the beneficial effects of the allogeneic HSCT result from an immune-mediated graft-versus-malignancy (GVM) effect and not from the high doses of chemotherapy administered in the preparative regimen. [5][6][7][8] Stable full or partial donor stem cell engraftment following the administration of a nonablative, reduced intensity preparative (RIT) regimen may also provide a platform for subsequent immune modulation to augment the GVM effect. [7][8][9] Compared to conventional, ablative preparative regimens, RIT regimens are generally associated with a decrease in TRM and other transplant-related complications. 3,7,10,11 However, despite a decrease in regimen-related toxicities, serious aGVHD and cGVHD remain a major cause of TRM and morbidi...

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Section: Survival and Disease Responsementioning

confidence: 99%

Section: Survival and Disease Responsementioning

confidence: 99%

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

Miller

Roberts

Chan

et al. 2004

Bone Marrow Transplant

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“…40 Patients who have received a purine nucleoside analog have reduced cellular-based immunity for at least 9 to 12 months after completion of therapy. [41][42][43] Addition of other immunosuppressive agents during this period of reduced T-cell numbers can further enhance the risk for infection. 44 Therefore, future combination strategies must consider the impact of adding agents to the purine nucleoside analogs.…”

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confidence: 99%

How I treat hairy cell leukemia

Grever

2010

Blood

141

124

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The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of ␣-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed this disease into a highly treatable form of leukemia, and patients with the classic form of this rare leukemia now have a near-normal life expectancy. However, other clinical entities mimicking this disease do not respond; thus, accurate diagnosis is important. Immunophenotypic features in classic hairy cell leukemia show that the leukemic cells express CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high percentage of durable complete remissions with modern therapy, the long-term disease-free survival curves have not reached a plateau. Many patients who achieve a complete remission by morphologic criteria have minimal residual disease demonstrable by either flow cytometry or immunohistochemical staining, and this population may be at higher risk for earlier relapse. Continued clinical research is essential to optimize therapy for this disease. (Blood. 2010;115:21-28) IntroductionIn 1958, Bouroncle et al described a series of patients with leukemic reticuloendotheliosis. 1 Although this collection of cases established that the previously described isolated reports actually represented a distinct hematologic malignancy, the classic manuscript contained a very thorough presentation of the many clinical facets of this disease now known as hairy cell leukemia (HCL). Furthermore, it established that therapeutic intervention was limited either to careful titration of alkylating agents or to splenectomy. The ability to alter the clinical course of the patients with this rare form of leukemia did not substantially change until the introduction of ␣-interferon in 1984. 2 Shortly thereafter, observations that a purine nucleoside analog (pentostatin) could induce a high degree of complete remissions (eg, 75%-89%) in this previously "untreatable" chronic leukemia changed the natural history of HCL in record time. [3][4][5][6][7][8] Another purine nucleoside analog (cladribine) produced remarkably high remission rates (eg, 91%) with a single course of therapy. 9,10 The outstanding results with this agent delivered as a single course of therapy led to cladribine being the initial therapy selected by most hematologists. Many of the initial studies with this agent excluded patients with active infection from enrollment, but studies from multiple institutions confirmed the high complete remission rate with this drug. [11][12][13][14] Thus, patients who are treated with either purine nucleoside analog as front-line therapy will achieve a high rate of complete remission (75%-90%). 7,10 The long-term studies reported at 5 to 10...

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“…An ADA inhibitor, DCF, has been widely used as a chemotherapeutic agent for leukemias such as adult T-cell leukemia (44) and hairy cell leukemia (45). However, it is known that the permeability of cell membranes to DCF is very low and that it does not penetrate into leukemia cells.…”

Section: Discussionmentioning

confidence: 99%

Adenosine Deaminase Activity of Insect-derived Growth Factor Is Essential for Its Growth Factor Activity

Homma¹,

Tanaka²,

Matsushita³

et al. 2001

Journal of Biological Chemistry

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Insect-derived growth factor (IDGF) was originally isolated from conditioned medium of NIH-Sape-4 cells derived from flesh fly embryos. Here we demonstrated that IDGF has adenosine deaminase activity. The substrate specificity of IDGF was similar to that of the mammalian cytoplasmic adenosine deaminase. The adenosine deaminase activity of IDGF was shown to be indispensable for its growth factor activity toward NIHSape-4 cells. We found that there are specific binding sites for IDGF on the surface of NIH-Sape-4 cells and that it binds to these sites with a K d value of 2.4 ؋ 10 ؊10

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Immunosuppressive effects of pentostatin.

Cited by 93 publications

References 16 publications

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

How I treat hairy cell leukemia

Adenosine Deaminase Activity of Insect-derived Growth Factor Is Essential for Its Growth Factor Activity

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