Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome

Dispenzieri, Angela; Lacy, Martha Q.; Hayman, Suzanne R.; Kumar, Shaji; Buadi, Francis K.; Dingli, David; Litzow, Mark R.; Gastineau, Dennis A.; Inwards, David J.; Elliott, Michelle A.; Micallef, Ivana N.; Ansell, Stephen M.; Hogan, William J.; Porrata, Luis F.; Johnston, Patrick A.; Afessa, Bekele; Bryce, Alan H.; Kyle, Robert A.; Gertz, Morie A.

doi:10.1111/j.1600-0609.2008.01037.x

Cited by 109 publications

(123 citation statements)

References 35 publications

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“…The incidence of ES after autotransplants in adults is 9-70% and correlates with the disease being treated. 2,3,[19][20][21][22][23][24] Pretransplant therapies also likely confound the incidence and presentation of ES. The highest incidences of ES are reported after autotransplants for breast cancer, 7,23 lymphomas other than Hodgkin lymphoma, 2 POEMS 24 and multiple sclerosis.…”

Section: Engraftment Syndromementioning

confidence: 99%

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Spitzer

2015

Bone Marrow Transplant

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Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is increasingly diagnosed. Common features include fever, pulmonary vascular leak, rash and organ dysfunction. Different diagnostic criteria likely account for the wide (7-90%) range of reported incidences. ES typically occurs within 4 days of granulocyte recovery although a recently described seemingly similar syndrome occurs 41 week before granulocyte recovery after umbilical cord blood cell transplants. Although the clinical manifestations of ES may be identical to those of acute GVHD, ES also has been well described in patients without acute GVHD. The data are conflicting as to whether ES is associated with a higher nonrelapse mortality and worse survival after HCT. The pathophysiology of ES is unclear, but endothelial injury and activated granulocytes in the setting of proinflammatory cytokines may be important. ES typically is self-limited, but, like acute GVHD, responds to corticosteroids. Because ES and acute GVHD may have overlapping features and response to therapy, these disease processes may often not be distinct events. Moreover, features of ES may overlap with those of drug-and radiation-induced toxicities and infection. Further research to better characterize the clinical spectrum and etiology of ES and to determine its relationship to GVHD is needed.

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Section: Engraftment Syndromementioning

confidence: 99%

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Spitzer

2015

Bone Marrow Transplant

116

128

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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%

“…Symptomatic progressions were rare, whereas radiographic and VEGF progressions were most common. Treatmentrelated morbidity and mortality can be minimized by recognizing and treating an engraftment-type syndrome characterized by fevers, rash, diarrhea, weight gain, and respiratory symptoms and signs that occur anytime between days 7 and 15 post-stem cell infusion [154]. A starting dose of prednisone ranging between 20 and 1,500 mg day 21 has been used.…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

“…The size of the M-protein is typically small making standard multiple myeloma response criteria inapplicable in most cases. In addition, patients can derive very significant clinical benefit in the absence of M-protein response [154,191]. Finally, despite the fact that the immunoglobulin-free light chains are elevated in 67-90% of POEMS patients, the ratio is normal in all but 13-18% [85,192] making the test of limited value for patients with POEMS syndrome.…”

Section: Monitoring Responsementioning

confidence: 99%

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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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“…In the past decade, melphalan-based therapy has made significant progress in the treatment of POEMS syndrome, including chemotherapy of melphalan and dexamethasone, 3 and highdose melphalan followed by autologous PBSC transplantation. [4][5][6] Several studies have reported that autologous transplantation could achieve excellent clinical responses in patients with POEMS syndrome. However, this therapy was associated with high mortality of about 8%.…”

Section: Introductionmentioning

confidence: 99%

PBSC mobilization in newly diagnosed patients with POEMS syndrome: outcomes and prognostic factors

Zhang

Duan

et al. 2012

Bone Marrow Transplant

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Autologous PBSC transplantation is a preferred treatment for patients with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS syndrome). However, data on stem cell mobilization in POEMS syndrome are limited. We retrospectively reviewed outcomes and factors prognostic of mobilization in newly diagnosed patients with POEMS syndrome. A total of 56 patients (41 men and 15 women) were included and the median age was 45 years (range, 24-62). All patients underwent mobilization with CY plus granulocyte CSF (G-CSF) (n ¼ 38) or G-CSF alone (n ¼ 18). The median total number of harvested CD34 þ cells was 2.01 Â 10 6 /kg (range, 0.18-9.0 Â 10 6 /kg). In all, 29 (51.8%) patients failed to yield more than 2 Â 10 6 /kg CD34 þ cells, and among them, 7 (12.5%) patients yielded o1 Â 10 6 /kg CD34 þ cells. The overall mobilization-related morbidity was 23.3% and acute renal failure was the most common complication during mobilization. Multivariate analysis showed that hepatomegaly (odds ratio 0.06, 95% confidence interval (CI) 0.01-0.43) and mobilization regimen of G-CSF alone (odds ratio 0.08, 95% CI 0.01-0.70) were independent prognostic factors for successful mobilization in POEMS syndrome. In conclusion, mobilization in newly diagnosed patients with POEMS syndrome is challenging with low yield of CD34 þ cells and high morbidity. Induction therapy before mobilization might improve the efficacy and safety of mobilization.

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Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome

Cited by 109 publications

References 35 publications

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

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

PBSC mobilization in newly diagnosed patients with POEMS syndrome: outcomes and prognostic factors

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