Response of Resistant Idiopathic Thrombocytopenic Purpura to Pulsed High-Dose Dexamethasone Therapy

Andersen, Judith C.

doi:10.1056/nejm199406023302203

Cited by 216 publications

(140 citation statements)

References 29 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…With prednisone or prednisolone given at a standard daily dose of around 1 mg/kg for 2 to 4 weeks, an initial response rate of 50% to 60% is generally obtained, but the long-term response rate without any therapy is very low (10%-25%). 3,[5][6][7] Moving from the Andersen experience, 15 concerning the use of pulsed HD-DXM given in resistant/refractory ITP with very satisfactory results, we planned a first pilot monocenter study with the aim of evaluating efficacy, safety, and tolerability of this treatment as first-line therapy in previously untreated adult ITP patients, according to a 6-cycle therapy schedule. The initial response rate was very encouraging (about 90%) and long-term response was about 68% (25/37, with 20 CR) in all evaluable patients (median FU 26 months).…”

Section: Discussionmentioning

confidence: 99%

“…13,14 The administration of pulsed high-dose dexamethasone (HD-DXM) at a dose of 40 mg/d given orally according to a 4-day course repeated each 28 days for 6 consecutive times in adult ITP refractory to several therapy lines, dates back to the mid-1990s. Indeed, in a small cohort of patients a response rate of 100% has been observed, 15 but in other studies, the same approach was not so successful. [16][17][18][19] Andersen's purpose 15 was based mainly on some considerations: (1) efficacy of pulsed corticosteroids in reducing immunoglobulin production in clonal B-cell disorders; (2) long half-life and good tolerability of DXM when given in high doses; and (3) very low cost of corticosteroids.…”

Section: Introductionmentioning

confidence: 95%

“…Indeed, in a small cohort of patients a response rate of 100% has been observed, 15 but in other studies, the same approach was not so successful. [16][17][18][19] Andersen's purpose 15 was based mainly on some considerations: (1) efficacy of pulsed corticosteroids in reducing immunoglobulin production in clonal B-cell disorders; (2) long half-life and good tolerability of DXM when given in high doses; and (3) very low cost of corticosteroids. Moreover, the efficacy associated with acceptable tolerability of pulsed HD-DXM was previously reported in the treatment of multiple myeloma.…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Mazzucconi

Fazi

Bernasconi

et al. 2006

Blood

233

181

View full text Add to dashboard Cite

In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate firstline treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (< 18 years, 36 of 42 ‫؍‬ 85.7%; > 18 years, 41 of 48 ‫؍‬ 85.4%, P ‫؍‬ not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P ‫؍‬ .018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial. (Blood.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Mazzucconi

Fazi

Bernasconi

et al. 2006

Blood

233

181

View full text Add to dashboard Cite

show abstract

“…Until now, ITP, at its chronic phase, is characterized by refractoriness to most therapies proposed. In contrast, the paper of Andersen (1994), which reported constant efficacy and limited side-effects of high-dose dexamethasone (40 mg/d for 4 d, every month, for six courses) in 10 patients with chronic refractory ITP was somewhat surprising. The study of Caulier et al (1995) did not confirm the results of this first report, since persistent remission was observed in only 1/10 patients treated with the same regimen.…”

Section: Therapy Of Chronic Autoimmune Purpura (Itp)mentioning

confidence: 94%

Correspondence

Sainty¹,

Arnoulet²,

Mj³

et al. 1997

Br J Haematol

View full text Add to dashboard Cite

We read with interest the report of Harada et al (1995) about a specific chromosome abnormality in CD7-positive acute myeloid leukaemia (AML):t(4;12)(q11;p13).The three cases (two AML-M0 and one AML-M2) evidenced a three-lineage dysplasia, absent or low myeloperoxidase activity, a normal or slightly decreased platelet count and a peripheral blood and bone marrow basophilia in two cases. The immunophenotype was CD7 þ , CD13 þ , CD34 þ , HLD-DR þ and the authors suggested that t(4;12)(q11;p13) is restricted to CD7-positive AML.Here we report the case of an 82-year-old man with a t(4;12)(q11;p13) and a CD7-negative AML with a unusual mature lymphoid morphological presentation in the peripheral blood. The peripheral blood showed 67 × 10 9 /l WBC with 80% small mature lymphoid-like cells, suggesting the diagnosis of chronic lymphocytic leukaemia (Fig 1A). The immunophenotype, performed on peripheral blood, was negative for T and B lymphoid markers and a complementary study showed positivity for CD117 (c-kit), CD13, CD33, CD11a, CD34 and CD56, with negativity for HLA-DR, CD16 and CD7. Immunological features were thus consistent with the HLA-DR ¹ , CD33 þ , CD56 þ , CD16 ¹ myeloid/natural killer cell entity (AML/NK; Scott et al, 1994). Bone marrow aspirate revealed 90% of cells with evident blastic morphology. Some of them presented rare small azurophilic granulations. Low myeloperoxidase activity (5%) was present in agreement with the FAB criteria for AML-M1.A t(4;12)(q11;p13) was evidenced in 20 mitoses by karyotype as a sole chromosomal abnormality using Q and R banding (Fig 1B-C). A dicentric (4;12) was eliminated by C banding.Only one case of AML with a mature lymphoid morphological presentation has been described (Matutes et al, 1987). The immunophenotype was CD13 þ , CD33 þ , CD117 þ , with positivity for CD7, negativity for CD16, but no data concerning HLA-DR and CD56. Karyo-type evidenced monosomy 5 and 21, t(2;13)(q23;q14), t(4;17)(p12;p11) and, as a secondary abnormality, a dicentric (4;12)(p12;?p12) with perhaps a breakpoint on 12p which was similar to our case.On the other hand, another case of t(4;12)(q11;p13) has been described in a relapse of AML-M4 secondary to a busulphan-treated polychthaemia vera, but the immunophenotype was not performed (den Nijs et al, 1989). In the three cases of t(4;12) described by Harada et al (1995), CD56, CD11a and CD16 were not tested but HLA-DR was positive.Altogether these data show that t(4;12)(q11;p13) is presently restricted to AML although possibly not to CD7 þ AML, as demonstrated by our case.Breakpoints in 12p13 have been described in myeloid malignancies and the TEL gene, a member of the family of ETS transcription factors located on 12p13, has been shown to be fused to the PDGF-Rb gene in t(5;12)(q33;p13) chronic myelomonocytic leukaemia (Golub et al, 1994), fused with the MN1 gene in t(12;22)(p13;q11) myeloproliferative disorders (Buijs et al, 1995) and disrupted in myelodysplastic syndromes with t(3;12)(q26;p13) (Raynaud et al, 1996). Whether the TEL gene and ...

show abstract

“…Although chemotherapy, with or without plasmapheresis, seems to be effective in some patients, it has potentially serious side effects [3,6,8,9]. Treatment with pulsed high-dose dexamethasone is usually well tolerated [1,2]. Based on the efficacy of dexamethasone as monotherapy in patients with multiple myeloma [1] and therapeutic resistant idiopathic trombocytopenic purpura [2], we treated patients with a progressive polyneuropathy associated with MGUS with pulsed high-dose dexamethasone (40 mg per day orally for 4 consecutive days once a month in 6 cycles).…”

mentioning

confidence: 99%

Pulsed high-dose dexamethasone treatment of polyneuropathy associated with monoclonal gammopathy

Notermans

Vermeulen²,

Lokhorst

et al. 1997

Journal of Neurology

View full text Add to dashboard Cite

Response of Resistant Idiopathic Thrombocytopenic Purpura to Pulsed High-Dose Dexamethasone Therapy

Cited by 216 publications

References 29 publications

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Correspondence

Pulsed high-dose dexamethasone treatment of polyneuropathy associated with monoclonal gammopathy

Contact Info

Product

Resources

About