Early diagnosis followed by front-line autologous peripheral blood stem cell transplantation for patients affected by POEMS syndrome

Laurenti, Luca; Matteis, Silvia De; Sabatelli, Mario; Conte, Amelia; Chiusolo, Patrizia; Sorà, Federica; Piccirillo, Nicola; Zà, Tommaso; Tarnani, Michela; Rossi, Elena; Leone, Giuseppe; Sica, Simona

doi:10.1016/j.leukres.2007.11.029

Cited by 31 publications

(31 citation statements)

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“…Six other cases of use with or after other alkylator based therapy yielded one death and 4 patients with improvement [22][23][24][25][26][27]176] High-dose chemotherapy with peripheral blood stem cell transplant can also be quite effective, but selection basis may confound these reports. Case series suggest 100% of patients achieve at least some neurologic improvement [18,54,87,140,[149][150][151][152][153][154][155][156][181][182][183][184][185]. Doses of melphalan ranging from 140 to 200 mg m 22 have been used, with the lower doses used for sicker patients.…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

POEMS syndrome: Update on diagnosis, risk‐stratification, and management

2015

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Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy.Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti‐VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 90:951–962, 2015. © 2015 Wiley Periodicals, Inc.

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Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

POEMS syndrome: Update on diagnosis, risk‐stratification, and management

2015

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“…by guest www.bloodjournal.org From For those patients well enough to tolerate high-dose melphalan (140 mg/m 2 to 200 mg/m 2 ) as conditioning for autologous peripheral blood stem cell transplantation (ASCT), ASCT is my first choice based on our own experience and reports from others. 19,39,[47][48][49][50][51][52][53][54][55][56][57][58][59] Because these patients have low tumor burden and their plasma cell clone is not rapidly proliferating, I do not typically recommend induction chemotherapy unless a patient is too sick to undergo ASCT immediately or if there are anticipated delays to bring him/her to ASCT. In the former instance, I typically use either cyclical cyclophosphamide (750 mg/m 2 intravenously every 3 weeks) with 4 to 5 days of corticosteroid or lenalidomide (15-25 mg orally days 1-21 every 28 days) with weekly dexamethasone.…”

Section: Targeting the Clonementioning

confidence: 99%

How I treat POEMS syndrome

Dispenzieri

2012

Blood

101

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POEMS syndrome is a paraneoplastic syndrome whose acronym stands for less than half of the defining features of the disease, that is, polyradiculoneuropathy, organomegaly, potentially including coexisting Castleman disease, endocrinopathy, monoclonal plasma cell neoplasm, and skin changes. The other important features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, elevated VEGF, and abnormal pulmonary function. The diagnosis is based on having both the polyradiculoneuropathy and the monoclonal plasma cell disorder, and at least 1 of the other 3 major criteria (Castleman disease, sclerotic bone lesions, or elevated VEGF) and at least one minor criterion. The diagnosis is often delayed with intervening incorrect diagnoses of chronic inflammatory demyelinating polyradiculoneuropathy, myeloproliferative disorder, and monoclonal gammopathy of undetermined significance. Prompt treatment directed at the underlying plasma cell clone produces dramatic responses in the majority of patients. Although there are no randomized clinical trial data to direct best therapy, for patients with disseminated disease, highdose chemotherapy with peripheral blood transplantation has yielded durable benefit, whereas radiation therapy is typically effective for patients with a more localized presentation. More universal recognition of and more scientific inquiry into the underpinnings of the disease will provide direction toward the best treatment strategies in the future. (Blood. 2012;119(24):5650-5658) Introduction POEMS syndrome, 1 also known as osteosclerotic myeloma, Takatsuki syndrome, 2 and Crow-Fukase syndrome, 3,4 is a rare paraneoplastic syndrome resulting from an underlying plasma cell disorder. There acronym POEMS refers to several, but not all, of the features of the syndrome: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. There are 3 important points that relate to this memorable acronym. First, not all of the features within the acronym are required to make the diagnosis (Table 1). Second, there are other important features not included in the POEMS acronym, including papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis, elevated VEGF levels, abnormal pulmonary function tests, and a predisposition toward thrombosis. Lastly, there is a Castleman disease variant of POEMS syndrome that may not be associated with a clonal plasma cell disorder. 5,6 Table 1 outlines the range of expected frequencies of each of the features based on the largest published series. 2,[7][8][9][10][11] The pathogenesis of the syndrome is not well understood. To date, VEGF is the cytokine that correlates best with disease activity, [12][13][14][15][16][17][18][19][20] although it may not be the driving force of the disease based on the mixed results seen with anti-VEGF therapy. 5,21-29 VEGF, which is expressed by osteoblasts, macrophages, tumor cells 30 (including plasma cells), 31,32 and megakaryocytes/pla...

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“…Case series, which include 100 patients in toto, suggest 100% of patients achieve at least some neurologic improvement [17,43,52,124,[127][128][129][130][131][132][133][134][135][136][137]. Anecdotally, responses are durable, but relapses have been reported [25,138].…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

“…A starting dose of prednisone ranging between 20 and 1,500 mg/day has been used. No evidence based recommendation can be given as to the appropriate dose, but personal experience would place the daily starting anywhere between 1 and 2 [39,[148][149][150][151] 50% of patients have significant clinical improvement Melphalan-Dexamethasone [146] 81% hematologic response rate; 100% with some neurologic improvement Corticosteroids [3,39,55,73,152] 15% of patients have significant clinical improvement High-dose chemotherapy with PBSCT [52,124,[130][131][132][133][134][135][136][137]139,[153][154][155][156][157][158] 100% of surviving patients have significant clinical improvement Thal after MP [159] No hematological response but improved ascites; stabilized PN, splenomegaly, pulmonary hypertension Thal 1 Dex after CAD [160] CD/POEMS: improved ascites, effusions, pulmonary hypertension, PN, renal function, IL-6 level Thal 1 Dex [161] N 5 9; VEGF improved in all; PN improved in 66%; stable in 33%; improved edema; no HCR Thal after VAD, CTX, bevacizumab [23] Improved cardiopulmonary status, but no improved PN and rising VEGF Lenalidomide 1 Dex [140] Improved ascites, PS, PN, VEGF, testosterone, pulmonary function tests Lenalidomide1 Dex [141] N59; all had hematologic response; clinical responses in all evaluable patients including PS, neurological syndrome, edema, and VEGF. Bortez1AD after VAD, CMP, and AD [142] Improved M-protein, VEGF, paresthesias, splenomegaly, effusions, muscle strength, gynecomastia, and skin changes...…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

POEMS syndrome: 2011 update on diagnosis, risk‐stratification, and management

Dispenzieri

2011

American J Hematol

119

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Disease overviewPOEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti‐VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 86:592–601, 2011. © 2011 Wiley‐Liss, Inc.

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Early diagnosis followed by front-line autologous peripheral blood stem cell transplantation for patients affected by POEMS syndrome

Cited by 31 publications

References 8 publications

POEMS syndrome: Update on diagnosis, risk‐stratification, and management

POEMS syndrome: Update on diagnosis, risk‐stratification, and management

How I treat POEMS syndrome

POEMS syndrome: 2011 update on diagnosis, risk‐stratification, and management

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