pentostatin

Summary

Summary: A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.

Top Publications

  1. Lamanna N, Kay N. Pentostatin treatment combinations in chronic lymphocytic leukemia. Clin Adv Hematol Oncol. 2009;7:386-92 pubmed
    ..b>Pentostatin has also been shown to have clinical activity in CLL and appears to be less toxic than its fludarabine ..
  2. Lamanna N, Kalaycio M, Maslak P, Jurcic J, Heaney M, Brentjens R, et al. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006;24:1575-81 pubmed
    ..Of the purine analogs active in CLL, pentostatin appears to be the least myelosuppressive...
  3. Panse J, Storb R, Storer B, Santos E, Wentzel C, Sandmaier B. Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation. Transplantation. 2005;80:1518-21 pubmed
    ..In contrast, grafts after 200 cGy TBI were durable in 11/12 recipients. We hypothesized that addition of pentostatin before transplantation could, in part, substitute for 100 cGy TBI...
  4. Higman M, Vogelsang G, Chen A. Pentostatin - pharmacology, immunology, and clinical effects in graft-versus-host disease. Expert Opin Pharmacother. 2004;5:2605-13 pubmed
    b>Pentostatin (deoxycoformycin), is one of a number of purine analogues. The drug was originally designed to mimic a form of severe combined immune deficiency, characterised by marked T lymphopenia but variable B cell function...
  5. Ravandi F, Faderl S. Complete response in a patient with adult T-cell leukemia (ATL) treated with combination of alemtuzumab and pentostatin. Leuk Res. 2006;30:103-5 pubmed
    ..Alemtuzumab with or without nucleoside analogs such as pentostatin may provide a role in this setting...
  6. Kay N, Geyer S, Call T, Shanafelt T, Zent C, Jelinek D, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007;109:405-11 pubmed
    Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously ..
  7. Pavletic S, Bociek R, Foran J, Rubocki R, Kuszynski C, Wisecarver J, et al. Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation. Transplantation. 2003;76:877-81 pubmed
    ..We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST...
  8. Dang N, Hagemeister F, Duvic M, Romaguera J, Younes A, Jones D, et al. Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes. Oncol Rep. 2003;10:1513-8 pubmed
    b>Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein...
  9. Goldberg J, Jacobsohn D, Margolis J, Chen A, Anders V, Phelps M, et al. Pentostatin for the treatment of chronic graft-versus-host disease in children. J Pediatr Hematol Oncol. 2003;25:584-8 pubmed
    Chronic graft-versus-host disease (cGVHD) is a major barrier to successful allogeneic stem cell transplantation. Pentostatin has been used to treat cGVHD in a small series of pediatric patients...

More Information

Publications62

  1. Hensel M, Villalobos M, Kornacker M, Krasniqi F, Ho A. Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Clin Lymphoma Myeloma. 2005;6:131-5 pubmed
    b>Pentostatin has demonstrated significant activity as a single agent in patients with low-grade B-cell and T-cell lymphomas and is less myelosuppressive than other purine analogues...
  2. Weiss M, Maslak P, Jurcic J, Scheinberg D, Aliff T, Lamanna N, et al. Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia. J Clin Oncol. 2003;21:1278-84 pubmed
    ..Of the purine analogs active in CLL, pentostatin may be least myelosuppressive...
  3. Maloisel F, Benboubker L, Gardembas M, Coiffier B, Divine M, Sebban C, et al. Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients. Leukemia. 2003;17:45-51 pubmed
    ..95. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses...
  4. Else M, Dearden C, Matutes E, Garcia Talavera J, Rohatiner A, Johnson S, et al. Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol. 2009;145:733-40 pubmed publisher
    ..We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long-term outlook. Median follow-up was 16 years...
  5. Reynolds C, Di Bella N, Lyons R, Hyman W, Richards D, Robbins G, et al. A Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia. Invest New Drugs. 2012;30:1232-40 pubmed publisher
    Uncontrolled studies comparing pentostatin (P), cyclophosphamide (C), and rituximab (R) (PCR) to fludarabine plus C+R (FCR) suggest similar efficacy with fewer infectious complications with PCR...
  6. Pidala J, Kim J, Roman Diaz J, Shapiro J, Nishihori T, Bookout R, et al. Pentostatin as rescue therapy for glucocorticoid-refractory acute and chronic graft-versus-host disease. Ann Transplant. 2010;15:21-9 pubmed
    ..We aimed to characterize the activity of pentostatin as rescue therapy for refractory GVHD...
  7. Bethge W, Kerbauy F, Santos E, Gooley T, Storb R, Sandmaier B. Extracorporeal photopheresis in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment. Bone Marrow Transplant. 2011;46:1382-8 pubmed publisher
    Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects, but have not been evaluated for their ability to enhance engraftment of hematopoietic stem cells...
  8. Alousi A, Weisdorf D, Logan B, Bolaños Meade J, Carter S, Difronzo N, et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009;114:511-7 pubmed publisher
    ..2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years)...
  9. Kay N, Wu W, Kabat B, Laplant B, Lin T, Byrd J, et al. Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia. Cancer. 2010;116:2180-7 pubmed publisher
    The combination of pentostatin (P), cyclophosphamide (C), and rituximab (R) achieved an overall response (OR) rate >90%, with >40% complete responses (CRs) in patients with untreated chronic lymphocytic leukemia (CLL)...
  10. Ravandi F, Aribi A, O Brien S, Faderl S, Jones D, Ferrajoli A, et al. Phase II study of alemtuzumab in combination with pentostatin in patients with T-cell neoplasms. J Clin Oncol. 2009;27:5425-30 pubmed publisher
    To examine the efficacy and safety of the combination of alemtuzumab and pentostatin in patients with T-cell neoplasms...
  11. Bolaños Meade J, Jacobsohn D, Margolis J, Ogden A, Wientjes M, Byrd J, et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol. 2005;23:2661-8 pubmed
    ..In steroid-refractory aGVHD, mortality is very high. Pentostatin, a potent inhibitor of adenosine deaminase, induces lymphocyte apoptosis and may be useful in the treatment of ..
  12. Dearden C, Else M, Catovsky D. Long-term results for pentostatin and cladribine treatment of hairy cell leukemia. Leuk Lymphoma. 2011;52 Suppl 2:21-4 pubmed publisher
    ..years we have collected data at our institution from 242 patients with hairy cell leukemia (HCL), treated with pentostatin (n?=?188) or cladribine (n?=?54), with a median follow-up of 16 years...
  13. Miller K, Roberts T, Chan G, Schenkein D, Lawrence D, Sprague K, et al. A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease. Bone Marrow Transplant. 2004;33:881-9 pubmed
    ..hematopoietic stem cell transplant (HSCT) received a regimen consisting of extracorporeal photopheresis, pentostatin, and reduced dose total body irradiation...
  14. Johnston J. Mechanism of action of pentostatin and cladribine in hairy cell leukemia. Leuk Lymphoma. 2011;52 Suppl 2:43-5 pubmed publisher
    b>Pentostatin (2'-deoxycoformycin; dCF) and cladribine (2-chlorodeoxyadenosine; CdA) are highly effective agents for the treatment of hairy cell leukemia...
  15. Tsimberidou A, Giles F, Duvic M, Fayad L, Kurzrock R. Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series. Cancer. 2004;100:342-9 pubmed
    The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies...
  16. Jacobsohn D, Gilman A, Rademaker A, Browning B, Grimley M, Lehmann L, et al. Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study. Blood. 2009;114:4354-60 pubmed publisher
    ..The Pediatric Blood and Marrow Transplant Consortium performed a phase 2 trial of pentostatin for steroid-refractory chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions...
  17. Braiteh F, Ng C, Kurzrock R. Refractory Hodgkin lymphoma responds to pentostatin (2'-deoxycoformycin). Leuk Lymphoma. 2006;47:373-5 pubmed
  18. Shanafelt T, Lin T, Geyer S, Zent C, Leung N, Kabat B, et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer. 2007;109:2291-8 pubmed
    ..5 times the upper limit of normal who met National Cancer Institute (NCI) 96-WG criteria for treatment received pentostatin (2 mg/m(2)), cyclophosphamide (600 mg/m(2)), and rituximab (375 mg/m(2))...
  19. Jacobsohn D, Chen A, Zahurak M, Piantadosi S, Anders V, Bolaños Meade J, et al. Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol. 2007;25:4255-61 pubmed
    ..There is no standard therapy for patients whose cGVHD does not resolve with corticosteroid treatment. Pentostatin, a potent inhibitor of adenosine deaminase, has activity in acute GVHD...
  20. Awan F, Kay N, Davis M, Wu W, Geyer S, Leung N, et al. Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab. Blood. 2009;113:535-7 pubmed publisher
    ..We investigated Mcl-1 protein expression prospectively as part of a phase 2 study evaluating the efficacy of pentostatin, cyclophosphamide, and rituximab in patients with untreated CLL...
  21. Cao T, Coutre S. T-cell prolymphocytic leukemia: update and focus on alemtuzumab (Campath-1H). Hematology. 2003;8:1-6 pubmed
    ..Prior to the appearance of pentostatin and alemtuzumab in clinical protocols, outcome for T-PLL patients was exceedingly poor with median survival ..
  22. Mittal S, Milner B, Johnston P, Culligan D. A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol. 2006;76:531-4 pubmed
    ..Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate. ..
  23. Quaresima M, Iacobelli S, Tempera S, Frattarelli N, Bizzoni L, Anaclerico B, et al. [Hairy cell leukemia: prognosis and treatment]. Clin Ter. 2006;157:105-9 pubmed
    ..First line treatment with purine analogues is correlated to prolonged PFS and DFS with respect to IFN; nevertheless no difference is observed in OS. ..
  24. Golomb H. Hairy cell leukemia: treatment successes in the past 25 years. J Clin Oncol. 2008;26:2607-9 pubmed publisher
  25. Fujita H, Koharazawa H, Nishida H, Terada S, Morishita T, Kuroyama Y, et al. [Successful treatment of hairy cell leukemia with pentostatin]. Rinsho Ketsueki. 2001;42:537-42 pubmed
    ..We diagnosed the patient as having European-American-type hairy cell leukemia. Pentostatin was administered at a dose of 5 mg/m2 weekly...
  26. Osuji N, Matutes E, Tjonnfjord G, Grech H, del Giudice I, Wotherspoon A, et al. T-cell large granular lymphocyte leukemia: A report on the treatment of 29 patients and a review of the literature. Cancer. 2006;107:570-8 pubmed
    ..An ORR of 67% (all CHR) was attained with pentostatin (n = 4 patients); recurrences developed after a median of 4.6 years...
  27. Aribi A, Huh Y, Keating M, O Brien S, Ferrajoli A, Faderl S, et al. T-cell large granular lymphocytic (T-LGL) leukemia: experience in a single institution over 8 years. Leuk Res. 2007;31:939-45 pubmed
    ..Other treatment modalities included single agent alemtuzumab, alemtuzumab combined with pentostatin, fludarabine, and combination of fludarabine and cyclophosphamide...
  28. Hassan R, Alewine C, Pastan I. New Life for Immunotoxin Cancer Therapy. Clin Cancer Res. 2016;22:1055-8 pubmed publisher
    ..However, new research has rejuvenated the field. Coadministration with a lymphocyte-depleting regimen of pentostatin and cyclophosphamide can delay antidrug antibody formation, increasing the number of treatment cycles that ..
  29. Matutes E, Brito Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood. 1991;78:3269-74 pubmed
    ..T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin. ..
  30. Lamanna N, Weiss M. Purine analogs in leukemia. Adv Pharmacol. 2004;51:107-25 pubmed
  31. Ho A, Thaler J, Mandelli F, Lauria F, Zittoun R, Willemze R, et al. Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1989;7:1533-8 pubmed
    Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL)...
  32. Johnson M, Johns D, Fridland A. 2',3'-Dideoxynucleoside phosphorylation by deoxycytidine kinase from normal human thymus extracts: activation of potential drugs for AIDS therapy. Biochem Biophys Res Commun. 1987;148:1252-8 pubmed
    ..Thus, dideoxynucleosides are activated by deoxycytidine kinase through a different catalytic interaction than occurs in 5'-activation of 3'-hydroxynucleosides by this enzyme. ..
  33. Pettitt A. Mechanism of action of purine analogues in chronic lymphocytic leukaemia. Br J Haematol. 2003;121:692-702 pubmed
  34. Gine E, Bosch F, Villamor N, Rozman M, Colomer D, Lopez Guillermo A, et al. Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association?. Leukemia. 2002;16:1454-9 pubmed
    ..Therefore, a large panel of monoclonal antibodies, including those necessary to detect CLL/SLL, should be employed when studying patients with HCL...
  35. Begleiter A, Pugh L, Israels L, Johnston J. Enhanced cytotoxicity and inhibition of DNA damage repair in irradiated murine L5178Y lymphoblasts and human chronic lymphocytic leukemia cells treated with 2'-deoxycoformycin and deoxyadenosine in vitro. Cancer Res. 1988;48:3981-6 pubmed
    ..These results suggest that 2'-deoxycoformycin/deoxyadenosine can function as a radiosensitizer, and this effect is associated with the cellular accumulation of dATP and inhibition of repair of DNA single strand breaks...
  36. Nishii K, Katayama N, Maeda H, Usui E, Takemitu T, Lorenzo V F, et al. Successful treatment with low-dose splenic irradiation for massive splenomegaly in an elderly patient with hairy-cell leukemia. Eur J Haematol. 2001;67:255-7 pubmed
    ..Here, we report an elderly Japanese HCL patient whose refractory massive splenomegaly responded well to low-dose splenic irradiation. ..
  37. Grigg A. 2'-Deoxycoformycin for hepatosplenic gammadelta T-cell lymphoma. Leuk Lymphoma. 2001;42:797-9 pubmed
    ..This is the second recent report of gammadelta T cell lymphoma responding to dCF, suggesting this agent may have a specific role in this condition. ..
  38. Gillis S, Amir G, Bennett M, Polliack A. Unexpectedly high incidence of hypoplastic/aplastic foci in bone marrow biopsies of hairy cell leukemia patients in remission following 2-chlorodeoxyadenosine therapy. Eur J Haematol. 2001;66:7-10 pubmed
    ..However, since the longest follow-up is less than 7 yr, the potential long-term significance of these findings, such as progressive bone marrow aplasia or dysplasia, may still be unrecognised. ..
  39. Braiteh F, Kurzrock R. CASE 1. Langerhans cell histiocytosis of the thyroid. J Clin Oncol. 2006;24:522-3 pubmed
  40. Honma Y, Niitsu N. Vidarabine and 2-deoxycoformycin as antileukemic agents against monocytic leukemia. Leuk Lymphoma. 2000;39:57-66 pubmed
    ..These results suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia. ..
  41. Stromski M, van Waarde A, Avison M, Thulin G, Gaudio K, Kashgarian M, et al. Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats. J Clin Invest. 1988;82:1694-9 pubmed
    ..Inhibition of adenosine deaminase during ischemia results in a injury similar to that seen after a shorter period of insult. ..
  42. Johnson S, Thomas W. Therapeutic potential of purine analogue combinations in the treatment of lymphoid malignancies. Hematol Oncol. 2000;18:141-153 pubmed
    The main purine analogues with activity against lymphoid malignancies are fludarabine, cladribine and pentostatin, all of which are active against slowly proliferating cells through their inhibition of DNA repair and therefore have ..
  43. Thaler J, Denz H, Dietze O, Gastl G, Ho A, Gattringer C, et al. Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin. Leuk Res. 1989;13:377-83 pubmed
    ..This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission. ..
  44. Brito Babapulle F, Huang D, Lavender P, Galton D, Catovsky D. Regression of intracerebral lesions in T prolymphocytic leukaemia treated with intravenous deoxycoformycin. Eur J Haematol. 1988;40:185-7 pubmed
    ..Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started. ..
  45. Cummings F, Crabtree G, Wiemann M, Spremulli E, Parks R, Calabresi P. Clinical, pharmacologic, and immunologic effects of 2'-deoxycoformycin. Clin Pharmacol Ther. 1988;44:501-9 pubmed
  46. Tedde A, Balis M, Ikehara S, Pahwa R, Good R, Trotta P. Animal model for immune dysfunction associated with adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1980;77:4899-903 pubmed
    ..4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man. ..
  47. Dearden C. T-cell prolymphocytic leukemia. Clin Lymphoma Myeloma. 2009;9 Suppl 3:S239-43 pubmed publisher
    ..The age and comorbidities of many of the patients has limited this option, but the growing use of nonmyeloablative transplantation has now widened the patient eligibility for this approach. ..
  48. Liu X, White T, Sawynok J. Potentiation of formalin-evoked adenosine release by an adenosine kinase inhibitor and an adenosine deaminase inhibitor in the rat hind paw: a microdialysis study. Eur J Pharmacol. 2000;408:143-52 pubmed
    ..The ability of an adenosine kinase inhibitor and an adenosine deaminase inhibitor to modulate this release is dependent on substrate adenosine concentrations. ..
  49. Iannitto E, Barbera V, Quintini G, Cirrincione S, Leone M. Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin. Br J Haematol. 2002;117:995-6 pubmed
  50. Calfa C, Lossos I, Ruiz P, Davis J. Ocular involvement as the initial manifestation of T-cell chronic lymphocytic leukemia. Am J Ophthalmol. 2007;144:326-9 pubmed
    ..Systemic evaluation established diagnosis of T-cell CLL. T-CLL is a rare disease with an aggressive clinical course. We present a case of T-cell intraocular lymphoma as the initial manifestation of an otherwise asymptomatic T-CLL. ..
  51. Ng J, Nolan B, Chan Lam D, Coup A, McKenna D. Successful treatment of aplastic variant of hairy-cell leukaemia with deoxycoformycin. Hematology. 2002;7:259-62 pubmed
    ..a patient with the aplastic variant of hairy cell leukaemia, successfully treated with the drug Deoxycoformycin(Pentostatin), is presented...
  52. Steurer M, Pall G, Richards S, Schwarzer G, Bohlius J, Greil R. Purine antagonists for chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2006;:CD004270 pubmed
    ..Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and hemolytic anemia. ..
  53. Smith W, Hubert D, Yazdi E, Holiat S, Bissell E, Watts L, et al. Complete remissions in chemotherapy of lung cancer models induced in mice by asbestos. Mt Sinai J Med. 2005;72:23-32 pubmed
    ..As a single agent, aziridinylbenzoquinone (AZQ) increased life span but gave no CRs. There were CRs of ASB XIII in all of 8 mice after toxic combined therapy with PCNU and AZQ. There were no CRs in 66 control mice bearing ASB XIII...