The "cited" column indicates whether the articles was cited in the reviews by Li 2013 ('L') or Dispenzieri 2014 ('D'). I have summarized clinical effects selectively (focusing on neuropathy).
I'm sure I've made mistakes, and that some of this is unclear. Please let me know when you find mistakes or unclarities, or have other suggestions, so that I can improve this! Thanks!
Harry Ide <harryide6@gmail.com>
-- last revised 6 August 2016
(I have excluded some articles. I assume that the reference to #168 on page 219 of Dispenzieri's 2014 review ('166-171') is a mistake, since it doesn't include any POEMS cases. Li 2011 and Zeng 2013 are in Chinese, and Medline has no abstract for either. Ji 2012 discusses 14 patients, and mentions that 1 had an auto, but doesn't discuss the process or results of the auto. Stefanelli 2012 mentions a POEMS patient who had an auto, but only to discuss a follow-up PET scan.)
Articles with four or more patients
| study | patients | follow-up (in months) | peri-transplant problems | result | cited | comments |
|---|---|---|---|---|---|---|
| Karam 2015 | 60 | mean 61 (4-162) | -peritransplant engraftment syndrome in 24 patients (40%) |
-all (except 1 who died early) had neurological improvement -before the auto, 27 required a wheelchair, 17 required a walker or foot brace; at the end of follow-up, no one was using a wheelchair, 23 were using a footbrace -14 patients required additional chemotherapy after auto, but none of them had clinical deterioration in neuropathy -6 patients died: 1 from POEMS, 1 from failure to engraft, 4 from other malignancies (2 myelodysplastic syndrome, 1 lymphoma, 1 metastatic lung cancer) |
-58 of the patients were previously reported in D'Souza 2012, which focuses on hematological effects, while this focuses on neurological effects |
|
| Patel 2014 | 7 | median 30 (10-83) | -engraftment syndrome (1) -fungal pneumonia (2) -pulmonary embolism (1) |
-clinical symptoms of all 7 resolved or significantly improved--for example, neuropathy improved significantly in 4 -1 patient died at +6 years because of a gastrointestinal bleed not related to POEMS -1 patient relapsed +3 years (treatment not stated) -6 'alive with controlled disease' |
apparently includes patients in Patel 2011 | |
| Nakaseko 2014 | 23 | median 51 | -engraftment syndrome (5), all responding well to corticosteroids | -22 patients showed improved clinical symptoms and reduced VEGF -'most' patients improved to walking without support; neuropathy 'gradually and continuously' improved -disease relapse in 5 patients -progression-free survival at 3 years 81%, 5-year progression-free survival 59.8% -overall survival at 3 years 96%, at 5 years 64.6% | ||
| Jang 2014 | 9 | 44 (8-94) | -engraftment syndrome |
-patient 4 died of disease progression at +8 months (progressive extravascular volume overload, and progressive neuropathy) -patient 3 died of pneumonia and respiratory failure at +4 months -three-year overall survival 77.8% -all survivors improved performance -patient 1: improved skin lesions and walking, decreased meds for peripheral neuropathy, resumed work -patient 2: improved to walking without assistance -patient 5: severe edema resolved quickly -patient 6: improved to walking without assistance (but no change in conduction velocities) -patient 7: reduced fluid; walks without assistance; stopped peripheral neuropathy meds -patient 8: worsened upper-limb sensory conduction velocities with no symptoms; can walk with cane -patient 9: can walk; no reduction in peripheral neuropathy meds |
-all patients started with poor performance status -used Dispenzieri's initial criteria, and not the current criteria |
|
| Gronier 2014 | 5 | ≥ 12 | -infection (4 patients) -culture-negative fever (2) -mucositis (4) -engraftment syndrome (1) | -significant improvement in neuropathy in all patients -serum [?] VEGF reduced in all patients (but rising in 3 between +6 months and +12 months) | ||
| Thoennissen 2012 | 5 | median 18 (11-120) | -no severe complications -no engraftment syndrome -mucositis, neutropenic fever, mild diarrhea -one patient developed reversible renal failure and pleural effusion | -all patients at least stabilized neuropathy -one patient had progressive disease at +2-1/2 years; a second auto resulted in clinical improvement -patient 1 became able to walk again; hepatosplenamegaly was stable -patient 2 became able to walk in the house but still needed a wheelchair for longer distances; spleen and liver size reduced -patient 3 was able to walk again; pulmonary function improved; still needs hormonal substitution; serum VEGF normalized; splenamegaly improving -patient 4 (two auto's); had stable peripheral neuropathy; serum VEGF rose after initial reduction following first auto, but was again reduced after second auto -patient 5 marked improvement in peripheral neuropathy; stable hepatomegaly | L | |
| D'Souza 2012 | 59 | median 45 (0-149) | -engraftment syndrome (22 patients) -incidence of periengraftment syndrome didn't differ with previous treatment with cyclophosphamide |
-3 deaths: (1) their first transplanted POEMS patient, who developed progressive lymphoma at +9 years and died at +13 years, with no evidence of POEMS at death, (2) of relapsed POEMS at +4 years, (3) not because of POEMS -14 patients with disease progression (usually radiological, or increasing VEGF; only 1 symptomatic progression) -5-year progression-free survival of 75%; 5-year overall survival 94% -2 patients developed secondary myelodysplastic syndrome (at +3 years and +7 years) -improved VEGF and extravascular fluid overload seen as early as +100 days -hematological and radiological responses usually seen by 1 year -maximal neurological response often not seen for 3 years -see this article for many more useful details | LD | -includes the patients in Hogan 2001, Dispenzieri 2004, and Dispenzieri 2008 -see Karam 2015 for more detailed about the neurological improvement (and for slightly longer follow-up) about mostly the same patients |
| Jimenez-Zepeda 2011 | 8 | median 54 (4-166) | -no engraftment syndrome (they suggest because of induction or mobilization with cyclophosphamide) -fever in 37.5%, diarrhea in 12.5%, weight gain ≥ 3% of baseline in 50% of patients -culture-negative fever (3 patients) -1 patient received a corticosteroid bolus for engraftment syndrome ('due to high-risk features including abnormal pulmonary function test and splenomegaly') -grade 2 oral mucositis in 2 patients -supplemental oxygen for 1 patient | -one patient showed progression at +100 months; treated with oral cytoxan-prednisone, which resulted in complete response -all evaluable patients benefitted clinically -peripheral neuropathy improved in all patients, dramatically in some | L | -used Spizter-Maiolino (2001 and 2003) criteria for engraftment syndrome -Dispenzieri et al. 2008 'took liberties with ... by loosening the time restriction of peripheral blood neutrophil reconstitution' [see D'Souza 2012 pp.56-7] |
| Cook 2011 | 127 | median 47.7 | -engraftment syndrome documented in 37% -two patients died before engraftment |
-non-relapse mortality at 1 year 3.3%, at 2 years 4.4%, at 5 years 7.7% -median progression-free survival was 106 months -five-year progression-free survival 73.5%, five-year overall survival 88.6% | L | -only the abstract is published -from the European society for Blood and Marrow Transplantation (EBMT) -this seems to be reprinted, with changes in the authors (!), in the 2013 ASH program (see program) |
| Duan 2010 (and Li 2013) |
9 | ? | -one patient died of severe infection and acute renal failure on day +9 |
-one patient died from diffuse tuberculosis infection at +18 months -all 8 evaluated patients showed neurological improvement -two patients had negative immunofixation electrophoresis; six were still positive after the auto -skin changes and peripheral edema improved in 5 of 6 patients -lymphadenopathy relieved in 1 patient -papilledema improved in 2 of 3 patients |
L | -Duan 2010 is in Chinese; this is based on the abstract and on Li's 2013 review, page 7, which adds a little information -one tandem transplant -Li's review says they're evaluating the results of more than 60 auto's for POEMS |
| Barete 2010 | 10 | mean 34 (14-87) | none mentioned | -neurologically, 6 patients improved, 3 stabilized, and 1 progressed -skin changes improved overall in 2 patients, and stabilized in 7 -VEGF-A declined after auto in 9 measured patients, and more in the 5 who improved neurologically than in the 4 who were stable or progressed | D | -article focuses on dermatological effects (and correlation with VEGF-A) -they treated one patient with bevacizumab at +12 months |
| Laurenti 2008 | 4 | median 40.5 (12-52) | -all patients had fever of unknown origin, treated with empirical antibiotics -one patient (with 'significantly deteriorated pulmonary function' before the auto) needed a ventilator for one month |
-all patients alive and improving neurologically -three patients with pre-auto sensory-motor peripheral neuropathy were able to walk -one patient with only sensory neuropathy had clear improvement -organomegaly and skin changes resolved in all patients -m-protein was eliminated in 2 patients, reduced in 2 -endocrinopathies were not improved |
LD | -perhaps the fevers were due to engraftment syndrome |
| Kuwabara 2008 | 9 | median 20 (8-49) | -no serious adverse effects |
-at +1 month, serum VEGF decreased rapidly in 8 of 9 patients -all patients improved substantially neurologically starting by +3 months -3 were chair- or bed-bound pre-auto; 2 became able to walk independently, and the third was walking with a stick -6 patients able to run -6 patients returned to work or nearly normal activity -neuropathy was still improving -serum VEGF reduced in all patients | LD | -includes the four patients published in Kuwabara 2006 -20 POEMS patients seen at Chiba Univ. Hosp. from 2003-6; 9 met criteria for autos |
| Abrisqueta 2007 | 4 | 48 | ? | -neurological improvement in all -m-protein and skeletal lesions decreased or disappeared |
-in Spanish; this is based only on the abstract (median follow-up from the chart in Créange 2008) |
|
| Jaccard 2002 | 5 | median 36 | -mucositis -'culture-negative neutropenic fever for 2 to 6 days' |
-patient 1 (who had tetraplegia) regained ability to walk, with some residual effects in lower limbs -patient 2 was cycling 15 km daily, with slight sensory loss in lower limbs distally -patient 3 had complete recovery except for adrenal insufficiency and hypertension -patient 4 had some residual motor effects in lower limbs -patient 5 recovered completely -no relapses |
LD | -perhaps the fever was engraftment syndrome -if I'm reading table 2 correctly, two patients had tandem autos (see the reference to a tandem transplant for one patient earlier on the page) -Créange 2008 p.690 reports the follow-up as median 32 months, but page 3059 says the median follow-up was 36 months |
Articles with fewer than four patients
| study | patients | follow-up (in months) | peri-transplant problems | result | cited | comments |
|---|---|---|---|---|---|---|
| Kim 2016 | 1 | 2 | none mentioned | dialysis stopped; serum creatinine reduced to 0.80; polyneuropathy improved (walking with walker) | -induction: 1 cycle of Bor-dex |
|
| Alvarez-Breckenridge 2015 | 1 | 2 | none mentioned | not completed | undergoing auto (as first-line treatment) after placement of a ventriculperitoneal shunt | |
| Smith 2015 | 1 | 9 months | none mentioned | improved symptoms; 9 months post-auto needed cane only for balance | [article focuses on diagnosis] | |
| Arana 2015 | 1 | 24 | no significant toxicity | 6 months post neuropathy and skin changes resolved; later negative immunofixation and all clinical manifestations resolved | ||
| Zeng 2013b | 1 | ? | ? | ? | -reports an auto after 4 cycles of bortezomib-dexamethasone, which produced significant clinical improvement (for example, he was able to return to walk); the article claims 'the autologous stem cell transplant was expected to cure POEMS syndrome' |
|
| Szturz 2013 | 1 | 4 | ? | -died at +4 months (no further details in abstract) |
-in Czech; this is based only on the abstract reports 10 patients with Castleman disease, 1 of whom had POEMS (with multicentric Castleman disease) |
|
| Ohashi 2013 | 1 | > 60 | ? | -relapse at +4 years 5 months (respiratory distress, extravascular fluid overload, increased VEGF and m-protein) -treated by lenalidomide-dexamethasone, resulting in complete remission, and improving clinically from 'total physical incapacity to being able to stand with slight assistance' | -in Japanese; this is based only on the abstract |
|
| Lestang 2013 | 1 | ? | ? | -complete response |
-given after relapse 5 months after ending treatment by lenalidomide-dexamethasone -abstract only |
|
| Kanashima 2013 | 1 | 10 | ? | -regained ability to walk without assistance -no m-protein on immunofixation |
-in Japanese; this is based only on the abstract |
|
| Ishii 2013 | 1 | 6 | -no engraftment syndrome | -improved to walking unassisted (from walking with a walker, after 4 cycles of bortezobib-dexamethasone) -plasma VEGF decreased from 463 pg/mL pre-bor-dex to 172, and to 69 pg/mL after auto -pulmonary hypertension improved -pleural and pericardial effusions disappeared after bor-dex -DLCO improved from 31% of predicted, to 60% after bor-dex, to 72% after auto |
||
| Vannata 2012 | 1 | 91 | ? | -improved neuropathy; was able to walk; pain disappeared -relapse at +6 yrs (anasarca, dyspnea, unable to walk, etc.); treated successfully with lenalidomide-dexamethasone (e.g. could walk independently after 10 cycles) |
||
| Matsuura 2012 | 1 | ? | -no engraftment syndrome (after induction with lenalidomide-dexamethasone) | -improved to walking independently | -in Japanese; this is based only on the abstract |
|
| Higashi 2012 | 1 | ? | ? | -renal function stabilized 'HDT was assumed to be effective in the renal lesions of this case' | -article focuses on repeated renal biopsies, and hardly mentions the auto |
|
| Adam 2012 | 1 | ? | ? | -'insufficient efficacy' led to treatment with thalidomide (not tolerated) and lenalidomide (which did not lead to remission) |
-in Czech; this is based only on the abstract -tandem transplant |
|
| Shindo 2011 | 1 | appx 7 yrs | -none mentioned, but: 'Post-tandem transplant complications were almost tolerable' [??] |
after 1st auto
-improved ability to walk -improved skin pigmentation -endocrinopathy unchanged; serum M-protein still detected after 2nd auto-hyperpigmentation and hemangioma resolved -no serum M protein on immunoelectrophoresis -normal serum EGF -continued sensory peripheral neuropathy -continued endocrinopathy -improved walking disorder -'return to normal life' | -tandem transplant; 2nd auto 5 months after first -diagnosed 16 months after diagnosis with solitary plasmacytoma -auto performed after adriamycin-dexamethasone did not improve neuropathy, with VEGF 'not completely normalized' |
|
| Nishihara 2011 | 1 | ? | -none mentioned |
-improved clinically -serum VEGF and m-protein improved -IgG4-related autoimmune pancreatitis did not improve |
-in Japanese; this is based only on the abstract |
|
| Isose 2011 | 1 | 28 | -none mentioned (but discussion is not detailed) |
-'systemic and neurological symptoms/signs improved' -could walk at +4 months -conduction velocities improved substantially |
||
| Hattori 2011 | 1 | 15 | -none mentioned |
-'relapse-free and in good condition' |
-in Japanese; this is based only on the abstract |
|
| Ohwada 2009 | 1 | 6 [?] | engraftment syndrome | -pre-auto bevacizumab improved his massive extravascular volume overload -improved from totally bedridden pre-auto to walking with a cane at +6 months -strength improved dramatically -serum VEGF decreased after auto -small m-protein detectable only on immunofixation |
||
| Mahdi-Rogers 2009 | 2 | -patient 1: 42 -patient 6: 11 |
-both experienced neutropenic sepsis | -patient 1: improved from able to walk 10 meters with a stick to able to walk a mile independently; abnormal sensation resolved -patient 6: initially improved neuropathy relapsed at about + 7 months, treated with second auto, with elimination of m-protein and neurological improvement; at +16 months from first auto could walk 4 km with a stick, and had reduced neuropathic pain |
-includes 4 patients treated for other diseases |
|
| Imai 2009 | 1 | 48 | -no significant complications |
-at +5 months, could stand without support; at +1 year, could 'walk with equipment' -reduced serum VEGF (2980 pg/ml to 1460 pg/ml) -relapse at +3 years (fluid overload, with serum VEGF not increasing) -treated by doxyrubicin + dexamethasone (with fluid retention mostly resolved), then thalidomide -stable at +1 year after relapse |
D | -'patient declined repeated auto-PBSCT' -relapse of the patient reported in Imai 2007 |
| Diaz-Betancur 2009 | 1 | 30 | -'culture[-positive?] fever', treated by antibiotics |
-totally autonomous -improved neuropathy -edema resolved -negative immunoelectrophoresis -significant improvement in lung function -asymptomatic |
||
| Ashawesh 2009 | 1 | 48 [?] | none mentioned | -at +4 years, adrenal function had recovered |
-article focuses only on adrenal recovery |
|
| Gütgemann 2008 | 1 | 10 yrs | ? |
-slow deterioration after auto -CVA in 2003 -died 'of generalized plasma cell myeloma' 10 yrs after diagnosis |
-auto was done in 1994, with total body irradiation -done after prednisone, melphalan, cyclophosphamide, alpha-interferon, thalidomide |
|
| Goto 2008 | 1 | 17 [?] | -'no serious complications' |
-at +6 months ascites and pleural effusion resolved; slight edema still present -neuropathy improved -serum VEGF normalized -at +17 months, could perform all activities of daily living by herself | ||
| Dietrich 2008 | 1 | 12 | -'well tolerated' |
-excellent clinical outcome; Karnofsky score improved to 90% at +1 yr |
-used bevacizumab to improve condition before transplant, which caused serum VEGF to drop from 9700 pg/mL to 61 pg/mL |
|
| Créange 2008 | 1 | 14 [?] | -neutropenic fever 'without bacteriological documentation', resolved with broad-spectrum antibiotics |
-regained ability to walk -major improvement of neuropathy -VEGF and other labs normalized | -perhaps engraftment syndrome |
|
| Chen 2008 | 1 | 6 | -transient neutropenic fever, mucositis, treated by broad-spectrum antibiotics |
-improved sensory and motor neuropathy -M-protein not detectable by immunofixation |
-perhaps engraftment syndrome |
|
| Samaras 2007 | 1 | 72 | -none mentioned |
-disease stabilized -relapse at +6 years (with neuropathy, extravascular volume overload, etc.) -treated with bevacizumab (Avastin), cyclophosphamide, steroids) -improved clinically after two courses of therapy -died after four courses of therapy (after multiorgan failure) | D | -article is about the relapse, not about the original transplant |
| Okada 2007 | 1 | 12 [?] | -none mentioned |
-retinal problems resolved -serum VEGF reduced (after transient increase following post-tranplant reduction) |
-focuses only on opthalmological problems |
|
| Nakamura 2007 | 1 | ? | -transient IgG-κ m-protein, thought to be due to normal immune reconstitution |
-VEGF normalized; m-protein disappeared -recovered from bedridden -no impairments |
-in Japanese; this is based only on the abstract |
|
| Giglia 2007 | 1 | 96 | -none mentioned |
-complete clinical remission, only minimal peripheral nerve effects; inconsistently detected subtle m-protein on immunofixation -relapse at +7 years (mild peripheral neuropathy, papilledema, skin angiomas, thrombocytosis, hypothyoroidism, elevated serum VEGF) -solitary bone lesion (C2 vertebral body), treated by radiation -at 1 year after radiation, unchanged bone lesion, stable clinically, elevated VEGF |
D | |
| Chahin 2007 | 1 | ? | ? | 'marked and rapid neurological improvement' | also had Charcot-Marie-Tooth 1A. had partial response to bevacizumab before auto | |
| Sanada 2006 | 1 | 12 [?] | -none mentioned |
-marked improvement in renal lesions -proteinuria resolved; M-protein undetectable on immunoelectrophoresis; VEGF normalized -edema resolved |
D | -no neuropathy pre-treatment, but progressive tremors |
| Kojima 2006 | 1 | > 20 | none |
-complete recovery from neuropathy -continued muscle weakness in right anterior tibialis |
D | -tandem autos (30 Mar 04, 4 Aug 04) |
| Kastritis 2006 | 2 | 6 | -neutropenic fever, mucositis |
-improved neuropathy and functional status -neuropathy was continuing to improve at +6 months |
D | -perhaps engraftment syndrome -primarily focuses on post-transplant angiogenesis and bone remodeling |
| Gupta 2006 | 1 | almost 84 | -uneventful |
-improved from unable to walking and participating in karate -absent deep tendon reflexes at knees and ankles -died of acute coronary syndrome almost 7 years post-auto -no evidence of progression at death |
||
| Chong 2006 | 1 | 16 | [not mentioned] |
-out of bed at 1 month -able to walk at 6 months |
auto briefly mentioned on p.691; focuses on MRI | |
| Ganti 2005 | 1 | 24 | -none mentioned |
-improved from wheelchair-bound to walking independently -improvement in nerve conduction studies, which still showed severe axonal/demyelinating peripheral neuropathy -stabilized arterial occlusive disease |
D | |
| Takai 2004 | 1 | ? | ? | -plural effusion resolved; performance status improved from bedridden |
D | in Japanese; this is based only on the abstract |
| Ozaki 2004 | 1 | 12 [?] | -at +5 months, Pneumocystis carinii infection, which responded to antiobiotics |
-extravascular volume overload resolved -m-protein not present; VEGF normalized -no improvement in neuropathy |
||
| Schliamser 2003 | 1 | 12 | -uneventful recovery |
-edema, lymphadenopathy, and hepatosplenomegaly resolved -pulmonary hypertension significantly improved -returned to normal activity (from disabling sensorimotor neuropathy) |
D | -only the abstract is published |
| Wiesmann 2002 | 1 | 72 | -neutropenic fever and severe mucositis | -significant neurological improvment; can walk short distances on crutches; upper limb EMGs normalized; peripheral edema resolved |
D | -no M-protein on immunofixation; article doesn't mention any other evidence of monoclonal plasma cell proliferation -transplant was done in April 1996 -the article doesn't mention whether the fever was culture negative (and hence perhaps engraftment syndrome) or culture positive |
| Soubrier 2002 | 2 | -patient 1: 120 -patient 2: 6 | -patient 1: none mentioned -patient 2: none mentioned | -patient 1: neuropathy improved; only sensorimotor deficits in feet; endocrinopathies resolved; serum VEGF normalized -patient 2: 'complete remission'; plasma VEGF normalized |
D | -patient 1 had an auto in June 1991 (not the first published, but the earliest published auto for POEMS) |
| Peggs 2002 | 2 | -patient 1: 24 -patient 2: 6 |
-patient 1: tender peri-anal lesion; febrile neutropenia resolved with broad-spectrum antibiotics -patient 2: severe mucositis; febrile neutropenia resolved with broad-spectrum antibiotics |
-patient 1: regained ability to walk and climb stairs; impaired balance; upper-limb function regained more slowly -patient 2: nerve conduction studies showed persistent motor neuropathy; ascites resolved; organomegaly improved |
D | -patient 1: auto came after irradiation of a solitary lesion, which may have caused improvement -the article doesn't say whether the fevers were culture negative (and hence perhaps engraftment syndrome) or culture positive |
| Rovira 2001 | 1 | 12 | -Pseudomonas spp bacteraemia (resolved with broad-spectrum antibiotics) |
-M-protein disappeared -abnormal labs resolved -EMGs improved -was wheelchair bound; at +1 year, could walk 'alone with effort' |
D | |
| Lambotte 2001 | 1 | 10 | -first auto: none mentioned -second auto: 'bad bone marrow reconstitution'; infections (successfully treated with antibiotics); anasarca (successfully treated except for persistent ascites) |
-first auto: stabilized kidney function; decreased proteinuria; decreased serum and urine m-protein -second auto: died of severe hypoalbuminemia and cachexia 10 months after first auto |
-probably a planned tandem auto, since they don't explain why they did a second auto, and don't point to problems after the first -the rare association of POEMS and a light-chain deposition disorder makes asking whether the patient had POEMS reasonable: the article reports polyneuropathy (described only as 'diminished pain and sensitivity on feet ... with profound asthenia' and with reduced motor and sensory conduction velocities on EMG), monoclonal κ light chains, no skeletal lesions, no discussion of Castleman's or VEGF, organomegaly, extravascular fluid overload, endocrinopathy (but only hypothyroidism), and skin changes; this does not meet Dispenzieri's current criteria (not developed when the article was written), since nothing meeting the "other major criteria" was documented, but it does meet her two mandatory major criteria (assuming the neuropathy counts) and the minor criterion | |
| Wong 1998 | 1 | 2 | -respiratory failure; Budd-Chiari syndrome |
-died from multiorgan failure on day +63 |
D |
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Electrolyte Blood Press. 2016 Jun;14(1):5-10. doi: 10.5049/EBP.2016.14.1.5. Epub 2016 Jun 30.
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