**4. Plasma cell leukaemia**

Plasma cell leukaemia is one of the most aggressive forms of MM. It is defined according to the Kyle criteria. Diagnosis is predicated on there being at least 20% plasma cells in a pe‐ ripheral blood smear and/or the absolute number of plasma cells in the peripheral blood ex‐ ceeding 2 G/l with a concomitant monoclonal gammopathy [Sher et al. 2010, Jimenez-Zepeda]. It should be noted that the presence of plasma cells in peripheral blood is symptomatic of several infectious diseases, e.g. septic shock, parvovirus B19 infection, infec‐ tious mononucleosis, and Dengue fever. These diseases, however, are not accompanied by the presence of monoclonal protein and the plasmacytosis abates with the other symptoms [Gawoski, Ooi 2003, Bai et al. 2006].

Plasma cell leukaemia is rare. It is estimated to constitute 0.5-3% of MM [Han et al. 2008]. Two forms of the disease should be distinguished: a primary form identified in the initial diagnosis; and a secondary form symptomatic of pre-existing classic MM. The primary form was more frequent than the secondary in previous analyses, but the number of patients with the primary and secondary forms is now similar [Sher et al.]. Complex cytogenetic abnor‐ malities are found in 70% of cases of plasma cell leukaemia. These usually include hypodi‐ ploidia and structural abnormalities of chromosomes 1, 13 and 14 that are similar in both forms of the disease [Fonseca et al. 2004, Chang et al. 2009, Colovic et al. 2008]. Plasma cell leukaemia is the most aggressive clinical form of MM. Patients usually manifest extraoss‐ eous infiltrations, often with the involvement of the central nervous system, and accompa‐ nied by *organomegaly* and lymphadenopathy. The aggressiveness of the disease is also demonstrated by the significantly increased activity of serum lactate dehydrogenase, high levels of β2-microglobulin (in 65% of patients > 6 mg/l) and low serum albumin levels.

The prognosis remains poor, especially in the secondary form, where it is a consequence of the progression of the disease and increasing *chemoresistance*. Moreover, resistance very quickly develops in patients with primary leukaemia, despite their initial response to treat‐ ment. The average survival time is 8 months for patients with the primary form and 2 months for those with the secondary form [Garcia-Sanz et al. 1999, Tiedemann et al. 2008]. Because of the low incidence of the disease, there are no randomized controlled trials and thus no therapeutic recommendations. Traditional schemes for treatment of MM are usually ineffective. Even though prolongation of survival time was reported in patients after mye‐ loablative chemotherapy assisted by autotransplantation, this treatment was less effective than it was in patients with the classic form of the disease. Allotransplantation is an alterna‐ tive, especially in the primary disease, which often affects younger people. Due to the limit‐ ed number of patients and lack of randomized studies, the effects of this treatment are difficult to assess, but previous reports indicate moderate effectiveness and high mortality (the mean survival time is 3 months) [Yeh et al. 1999].

New drugs, such as proteasome inhibitors and immunomodulatory drugs, are promising, although the effectiveness of this treatment remains unsatisfactory. As thalidomide is of lim‐ ited efficacy and seems to have no significant effect on prolonging survival time in patients with plasma cell leukaemia (reported mean survival time is 3 months) [Petrucci et al. 2007], other authors have been presenting more promising data (survival time up to 14 months) [Johnston, Abdalla 2002]. The use of lenalidomide has enabled a response to be obtained in individual patients, as with resistance to other schemes, but this usually lasts 4-5 months [Musto et al. 2008, Benson and Smith 2007]. The results of bortezomib treatment are slightly more promising. This therapy, especially the combination therapy (VDT-PACE), enables a response to be obtained in more than 90% of patients, including those in whom the disease is initially chemoresistant. Mean survival time is 7-12 months [Albarracin, Fonseca 2011, Musto et al. 2007], although survival times of up to 20 months have also been reported [Sher et al. 2010, Ali et al. 2007]. Bortezomib appears to be able to overcome the adverse effects of cytogenetic abnormalities [Katodritou et al. 2009] – as it does with classic MM – and should therefore be considered a first-line treatment in patients with plasma cell leukaemia.

## **5. POEMS syndrome**

clinical features of multiple myeloma such as hypercalcemia, renal failure and osteolytic fo‐ ci, support a diagnosis of IgM MM much more frequently than a diagnosis of WM. These differential diagnostics may not be easy. Cytogenetic tests are helpful in these situations. Re‐ cent study results indicate that the presence of translocation t(11;14) associated with deregu‐ lation of cyclin D1 is specific for MM, but not for WM [Avet-Loiseau et al. 2003]. Another differentiating feature is that 6q deletion istypical of WM [Schop et al. 2006]. Some authors, however, indicate the limited sensitivity of cytogenetic testing in diagnosing MM IgM and therefore seek other differential diagnostic tests [Schuster et al. 2010]. One would be an in‐ creased expression of interleukin-1b (IL-1b). This substance is responsible for the increased production of interleukin 6 (IL-6) reported in patients with MM [Donovan et al. 2002]. The treatment of patients with IgM MM does not differ substantially from the treatment of pa‐ tients with the classic form of MM. Some studies however, indicate a significantly worse prognosis compared with the classic forms, i.e. a much shorter survival time and progres‐ sion-free time in patients with the rare form of MM [Morris et al. 2010]. Mean survival time is 30 months and myeloablative chemotherapy does not alter this prognosis [Reece et al.

IgE myeloma is very rarely detected. Several cases of this variant have been described [In‐ vernizzi et al. 1991, Hagihara et al. 2010, Chiu et al. 2010]. It manifests itself by the frequent presence of plasma cells in peripheral blood, osteoblastic lesions, hepatosplenomegaly and amyloidosis. The clinical course of this form of MM is usually aggressive and patients have a shorter survival time than those with the classic forms (16 months on average). This may

Plasma cell leukaemia is one of the most aggressive forms of MM. It is defined according to the Kyle criteria. Diagnosis is predicated on there being at least 20% plasma cells in a pe‐ ripheral blood smear and/or the absolute number of plasma cells in the peripheral blood ex‐ ceeding 2 G/l with a concomitant monoclonal gammopathy [Sher et al. 2010, Jimenez-Zepeda]. It should be noted that the presence of plasma cells in peripheral blood is symptomatic of several infectious diseases, e.g. septic shock, parvovirus B19 infection, infec‐ tious mononucleosis, and Dengue fever. These diseases, however, are not accompanied by the presence of monoclonal protein and the plasmacytosis abates with the other symptoms

Plasma cell leukaemia is rare. It is estimated to constitute 0.5-3% of MM [Han et al. 2008]. Two forms of the disease should be distinguished: a primary form identified in the initial diagnosis; and a secondary form symptomatic of pre-existing classic MM. The primary form was more frequent than the secondary in previous analyses, but the number of patients with the primary and secondary forms is now similar [Sher et al.]. Complex cytogenetic abnor‐ malities are found in 70% of cases of plasma cell leukaemia. These usually include hypodi‐ ploidia and structural abnormalities of chromosomes 1, 13 and 14 that are similar in both

2010, Schuster et al. 2010].

246 Multiple Myeloma - A Quick Reflection on the Fast Progress

**4. Plasma cell leukaemia**

[Gawoski, Ooi 2003, Bai et al. 2006].

be a result of a delayed diagnosis [Macro et al. 1999].

The syndrome was first described in 1956 and was originally named the Crow–Fucasi syn‐ drome. Since 1980, it has been known by the acronym POEMS, derived from the symptoms polyneuropathy, enlarged internal organs (organomegaly), endocrine disorders, monoclonal protein and skin changes.

The pathogenesis of POEMS syndrome is complex and not fully understood. The starting point must be the mutation of the plasma cells producing the light chains (usually λ) as this is what causes its clonal expansion. Karyotype tests of plasma cells usually reveal aneuploi‐ dy [Rose et al. 1997] and del13 [Bryce et al. 2007]. Whether a neoplastic clone produces its characteristic symptoms through the direct action of monoclonal protein on some target molecules and the secretion of various cytokines from neoplastic cells, or whether it hap‐ pens in an indirect manner, is not precisely known. It is believed that high levels of pro-an‐ giogenic and pro-inflammatory cytokines, especially IL-1β, TNF-α, IL-6 and a concentration of vascular endothelial growth factor (VEGF) are essential to the development of the clinical symptoms of POEMS syndrome [Gherardi et al. 1996, Hitoshi et al. 1994].

Gait disorders may appear later. This process is progressive and movement is difficult in 50% of patients. This can eventually cause disability. Bone pain and pathologic fractures are

Rare Manifestations of Multiple Myeloma http://dx.doi.org/10.5772/53385 249

About 1/3 of patients develop ascites and fluid in the pleural cavities [Dispenzieri et al. 2007]. In 50% of patients, the liver, and less frequently the spleen and the lymph nodes, is enlarged. A histopathological examination of the enlarged lymph node often indicates an‐ giofollicular lymph node hyperplasia (Castleman's disease) [Dispenzieri et al. 2003, Naka‐ nishi et al. 1984]. Some patients may develop venous and arterial thrombosis [Kang et al. 2003]. Impaired secretion of endocrine glands, most commonly hypogonadism, hypothyr‐ oidism, glucose metabolism and adrenal insufficiency, is diagnosed in about 84% of pa‐ tients. Most patients have impaired secretion in four or more endocrine glands. This may be

Because the predominant symptom is polyneuropathy, patients with POEMS syndrome are initially referred to neurologists - usually with suspected Guillain-Barré syndrome or chron‐

Once the monoclonal protein accompanying the polyneuropathy has been detected, a differ‐

The concentration of VEGF is one of the most sensitive tests to differentiate POEMS syn‐ drome from the other diseases mentioned above. The plasma of patients with POEMS syn‐ drome has a high VEGF concentration. VEGF concentration in patients with the other

The rare incidence of POEMS syndrome and the lack of definitive knowledge as to its causes mean that there are no standards of treatment. For the same reason, there are no random‐ ized clinical trial results to evaluate the effectiveness of any given method of treatment. Methods of treating POEMS syndrome patients have mainly been devised from clinical re‐ ports, case reports and retrospective observations (usually at a single centre), and the experi‐

Radiotherapy is the treatment of choice for POEMS syndrome patients with isolated bone lesions. If there are numerous bone changes and these coexist with other symptoms typical of POEMS syndrome, it is recommended that patients be treated similarly to those with MM. In older patients, the treatment is based on alkylating drugs, while the therapy for younger patients includes high-dose chemotherapy-assisted auto-SCT [Dispenzieri et al.

The final confirmation of the hypothesis that VEGF is the major cytokine responsible for the development of POEMS syndrome, will have a significant impact on changing the way that POEMS patients are treated; the way which will be predominantly focused on VEGF..Nei‐ ther intravenous immunoglobulins nor plasmapheresis treatments benefit patients with PO‐ EMS syndrome [Dispenzieri et al. 2007]. The concomitant treatment with plasmapheresis and corticosteroids was found to be more effective [Ku et al. 1995]. Melphalan is the drug that has been used to treat *dyscrasias* the longest. The results of retrospective studies, in

rare. Other symptoms include progressive weight loss and muscle atrophy.

accompanied by failure of the gonads, thyroid, pancreas and adrenal glands.

ential diagnosis should include AL, monoclonal gammopathy and MM.

diseases mentioned above is low [Gherardi et al. 1996, Watanabe et al. 1998].

ic inflammatory demyelinating polyradiculoneuropathy.

ence gained from treating other plasma cells *dyscrasias*.

2003].

VEGF is considered to be the most important cytokine responsible for the development of POEMS syndrome. This is the cytokine that reacts with endothelial cells and causes the rap‐ id and reversible increase in vascular filtration essential to angiogenesis and osteogenesis [Endo et al. 2002, Soubrier et al. 1997]. The increased production of VEGF is also a result of high concentrations of IL-1 and IL-6 [Soubrier et al. 1997]. VEGF 165 isoform is most com‐ monly diagnosed. The concentration of VEGF correlates with the progression of the disease, but does not depend on the concentration of monoclonal protein [Watanabe et al. 1998].

POEMS syndrome is very rare. The incidence in Japan is 3 cases per million people per year [Arimura et al. 2007], and this is estimated to be even less in Western Europe and the United States of America. The peak incidence of POEMS syndrome occurs during the fifth and the sixth decades of life [Dispenzieri et al. 2007]. POEMS syndrome is a chronic disease and some patients live more than 10 years. Dispenzieri et al. have found that the mean survival time of patients with POEMS is 13.8 years [Dispenzieri et al. 2003]. In turn, Gherardi et al. have found that 7 out of 15 patients with POEMS syndrome live 5 years or more, including one case of 25 years [Gherardi et al. 1991].

The criteria for diagnosing POEMS syndrome are summarized in Table 3.

The characteristic symptoms of POEMS syndrome should have a temporal relationship. The most important symptom, i.e. the one that enables POEMS to be differentiated from other plasma cell dyscrasias, is the ascertainment of single or multiple osteosclerotic changes. A conclusive diagnosis of POEMS syndrome is unlikely in the absence of bone changes. Skin changes, most commonly hypertrichosis and hyperpigmentation, may occur in POEMS pa‐ tients. Enlarged mammary glands and testicular atrophy may occur in men. Peripheral blood count abnormalities, especially thrombocythemia and polyglobulia, are frequently de‐ tected by morphological examinations.

The concentrations of serum monoclonal protein and the level of Bence-Jones protein in urine are lower than in patients with MM. Renal failure, high calcium plasma concentration, and pathological bone fractures are rarely observed. The percentage of plasma cells is usual‐ ly less than 5% in bone marrow examinations. High concentrations of IL-1β, TNF-α, IL-6 and VEGF in serum are typical of POEMS [Soubrier et al. 1997].

Polyneuropathy is the predominant clinical symptom (100% of patients with POEMS syn‐ drome) [Kelly Jr. et al. 1983]. Initially, sensory disturbances occur mainly in the lower limbs. Gait disorders may appear later. This process is progressive and movement is difficult in 50% of patients. This can eventually cause disability. Bone pain and pathologic fractures are rare. Other symptoms include progressive weight loss and muscle atrophy.

The pathogenesis of POEMS syndrome is complex and not fully understood. The starting point must be the mutation of the plasma cells producing the light chains (usually λ) as this is what causes its clonal expansion. Karyotype tests of plasma cells usually reveal aneuploi‐ dy [Rose et al. 1997] and del13 [Bryce et al. 2007]. Whether a neoplastic clone produces its characteristic symptoms through the direct action of monoclonal protein on some target molecules and the secretion of various cytokines from neoplastic cells, or whether it hap‐ pens in an indirect manner, is not precisely known. It is believed that high levels of pro-an‐ giogenic and pro-inflammatory cytokines, especially IL-1β, TNF-α, IL-6 and a concentration of vascular endothelial growth factor (VEGF) are essential to the development of the clinical

VEGF is considered to be the most important cytokine responsible for the development of POEMS syndrome. This is the cytokine that reacts with endothelial cells and causes the rap‐ id and reversible increase in vascular filtration essential to angiogenesis and osteogenesis [Endo et al. 2002, Soubrier et al. 1997]. The increased production of VEGF is also a result of high concentrations of IL-1 and IL-6 [Soubrier et al. 1997]. VEGF 165 isoform is most com‐ monly diagnosed. The concentration of VEGF correlates with the progression of the disease, but does not depend on the concentration of monoclonal protein [Watanabe et al. 1998].

POEMS syndrome is very rare. The incidence in Japan is 3 cases per million people per year [Arimura et al. 2007], and this is estimated to be even less in Western Europe and the United States of America. The peak incidence of POEMS syndrome occurs during the fifth and the sixth decades of life [Dispenzieri et al. 2007]. POEMS syndrome is a chronic disease and some patients live more than 10 years. Dispenzieri et al. have found that the mean survival time of patients with POEMS is 13.8 years [Dispenzieri et al. 2003]. In turn, Gherardi et al. have found that 7 out of 15 patients with POEMS syndrome live 5 years or more, including

The characteristic symptoms of POEMS syndrome should have a temporal relationship. The most important symptom, i.e. the one that enables POEMS to be differentiated from other plasma cell dyscrasias, is the ascertainment of single or multiple osteosclerotic changes. A conclusive diagnosis of POEMS syndrome is unlikely in the absence of bone changes. Skin changes, most commonly hypertrichosis and hyperpigmentation, may occur in POEMS pa‐ tients. Enlarged mammary glands and testicular atrophy may occur in men. Peripheral blood count abnormalities, especially thrombocythemia and polyglobulia, are frequently de‐

The concentrations of serum monoclonal protein and the level of Bence-Jones protein in urine are lower than in patients with MM. Renal failure, high calcium plasma concentration, and pathological bone fractures are rarely observed. The percentage of plasma cells is usual‐ ly less than 5% in bone marrow examinations. High concentrations of IL-1β, TNF-α, IL-6

Polyneuropathy is the predominant clinical symptom (100% of patients with POEMS syn‐ drome) [Kelly Jr. et al. 1983]. Initially, sensory disturbances occur mainly in the lower limbs.

symptoms of POEMS syndrome [Gherardi et al. 1996, Hitoshi et al. 1994].

The criteria for diagnosing POEMS syndrome are summarized in Table 3.

and VEGF in serum are typical of POEMS [Soubrier et al. 1997].

one case of 25 years [Gherardi et al. 1991].

248 Multiple Myeloma - A Quick Reflection on the Fast Progress

tected by morphological examinations.

About 1/3 of patients develop ascites and fluid in the pleural cavities [Dispenzieri et al. 2007]. In 50% of patients, the liver, and less frequently the spleen and the lymph nodes, is enlarged. A histopathological examination of the enlarged lymph node often indicates an‐ giofollicular lymph node hyperplasia (Castleman's disease) [Dispenzieri et al. 2003, Naka‐ nishi et al. 1984]. Some patients may develop venous and arterial thrombosis [Kang et al. 2003]. Impaired secretion of endocrine glands, most commonly hypogonadism, hypothyr‐ oidism, glucose metabolism and adrenal insufficiency, is diagnosed in about 84% of pa‐ tients. Most patients have impaired secretion in four or more endocrine glands. This may be accompanied by failure of the gonads, thyroid, pancreas and adrenal glands.

Because the predominant symptom is polyneuropathy, patients with POEMS syndrome are initially referred to neurologists - usually with suspected Guillain-Barré syndrome or chron‐ ic inflammatory demyelinating polyradiculoneuropathy.

Once the monoclonal protein accompanying the polyneuropathy has been detected, a differ‐ ential diagnosis should include AL, monoclonal gammopathy and MM.

The concentration of VEGF is one of the most sensitive tests to differentiate POEMS syn‐ drome from the other diseases mentioned above. The plasma of patients with POEMS syn‐ drome has a high VEGF concentration. VEGF concentration in patients with the other diseases mentioned above is low [Gherardi et al. 1996, Watanabe et al. 1998].

The rare incidence of POEMS syndrome and the lack of definitive knowledge as to its causes mean that there are no standards of treatment. For the same reason, there are no random‐ ized clinical trial results to evaluate the effectiveness of any given method of treatment. Methods of treating POEMS syndrome patients have mainly been devised from clinical re‐ ports, case reports and retrospective observations (usually at a single centre), and the experi‐ ence gained from treating other plasma cells *dyscrasias*.

Radiotherapy is the treatment of choice for POEMS syndrome patients with isolated bone lesions. If there are numerous bone changes and these coexist with other symptoms typical of POEMS syndrome, it is recommended that patients be treated similarly to those with MM. In older patients, the treatment is based on alkylating drugs, while the therapy for younger patients includes high-dose chemotherapy-assisted auto-SCT [Dispenzieri et al. 2003].

The final confirmation of the hypothesis that VEGF is the major cytokine responsible for the development of POEMS syndrome, will have a significant impact on changing the way that POEMS patients are treated; the way which will be predominantly focused on VEGF..Nei‐ ther intravenous immunoglobulins nor plasmapheresis treatments benefit patients with PO‐ EMS syndrome [Dispenzieri et al. 2007]. The concomitant treatment with plasmapheresis and corticosteroids was found to be more effective [Ku et al. 1995]. Melphalan is the drug that has been used to treat *dyscrasias* the longest. The results of retrospective studies, in which melphalan was mainly used in combination with prednisone (the treatment duration was 12-24 months), indicate that a response to the treatment was obtained in 40% of patients [Dispenzieri et al. 2003]. Cyclophosphamide allows for remission of the disease in a limited number of patients. This treatment may be used in young patients who are candidates for auto-SCT.

tleman disease, a condition that can accompany POEMS syndrome. Other drugs used to treat POEMS syndrome patients include interferon α [Coto et al. 1991], tamoxifen, trans reti‐ noic acid, thalidomide, ticlopidine, argatroban and strontium (89Sr) [Dispenzieri et al. 2007].

Rare Manifestations of Multiple Myeloma http://dx.doi.org/10.5772/53385 251

Lenalidomide seems to be one of the most promising immunomodulatory drugs to treat PO‐

High dose chemotherapy assisted auto-SCT remains the best therapeutic method, although

Sweet's syndrome is one of the paraneoplastic syndromes that may accompany MM. This is a group of symptoms including granolocytosis, fever and painful erythematous skin changes caused by skin *granulocytic* infiltrations that subside following treatment with corti‐ costeroids [Paydas et al. 1993]. These changes are also found in the mouth, the joints and the internal organs. Sweet's syndrome is extremely rare (0.25% of patients with MM) and is most likely caused by an increased sensitivity to the growth factor. This can be explained by an increased production of interleukin 6 (IL-6) [Bayer-Garner, Cottler-Fox, Smoller 2003].

Bullous epidermal separation (epidermolisis bullosa) may also coexist with MM. This is as‐ sociated with the production of IgG antibodies against the *non-collagenous* domain of type VII collagen. This leads to the formation of subepidermal bubbles and secondary ulcers [Radfar 2006]. Pemphigus has a similar clinical picture. This is a rare complication observed in MM patients and is usually associated with IgA MM. This disease develops extremely rarely and is sometimes also associated with gammopathy of undetermined significance. It has been suggested that treatment should include bortezomib [Adam et al. 2010]. There are many skin symptoms associated with monoclonal gammopathy: leukocytoclastic vasculitis, pyoderma gangrenosum and Schnitzler syndrome. These, however, are rare and discussing

The cause of MM remains unknown [Lynch et al. 2008, Alexander et al. 2007, Morgan, Da‐ vies, Lineta 2002]. It seems that the hereditary cause is negligible, although family cases of this cancer have been observed. It has also been described in connection with gammopathy of undetermined significance [Lynch et al. 2008]. Large population studies also indicate that MM, prostate cancer and malignant melanoma run in families, as do central nervous system neoplasms, although the results of some studies do not confirm this [Eriksson, Hallberg 1992, Camp, Werner, Cannon-Albright, 2008]. The risk of familial MM is small. It is estimat‐ ed that the probability of first-degree relatives developing MM is 3.2 per 1000 cases and

The effectiveness of these drugs is limited and further clinical trials are required.

EMS syndrome, but further clinical studies are required [Dispenzieri et al. 2007].

**6. Rare paraneoplastic syndromes accompanying myeloma**

them is beyond the scope of this chapter [Harati et al. 2005].

**7. Family myeloma**

it also has the highest mortality rate.

The results of high-dose chemotherapy-assisted auto-SCT are promising [Sanada et al. 2006], as a response is obtained in over 90% of patients (Table 4). Transplant related mortality is determined to be approximately 7%. This is higher than in MM patients treated with auto-SCT and lower than in AL patients treated with auto-SCT [Gertz et al. 2002]. High dose che‐ motherapy assisted auto-SCT reduces the symptoms of polyneuropathy. When combined with radiotherapy, this reduction can last months or even years [Ganti et al. 2005]. The clini‐ cal response to the treatment correlates more closely to the VEGF concentration than to the monoclonal protein level [Nakano et al. 2001]. A *complete* haematological remission is not re‐ quired to obtain a clinical improvement. The effectiveness of the most common ways of treating patients with POEMS syndrome is shown in Table 4.


Auto-SCT (*auto-stem cells transplantation*) – autologous transplantation of the stem cells obtained from peripheral blood.

**Table 4.** The effectiveness of the most commonly used treatments in patients with POEMS syndrome.

Apart from the methods of treating POEMS syndrome mentioned above, there are few re‐ ports on the effectiveness of therapy combined with bevacizumab and thalidomide in pa‐ tients diagnosed with a relapse of POEMS syndrome after auto-SCT. The combination of cyclophosphamide, dexamethasone and bevacizumab is another example of a modern com‐ bination therapy, described by Samaras et al., to treat POEMS syndrome relapse after auto-PBSCT [Badros et al. 2005, Straume et al. 2006]. There are also case reports describing the treatment of patients with POEMS syndrome using lenalidomide [Dispenzieri et al. 2007]. Recently, Szturz et al. [2012] reported on the successful application of lenalidomide in Cas‐ tleman disease, a condition that can accompany POEMS syndrome. Other drugs used to treat POEMS syndrome patients include interferon α [Coto et al. 1991], tamoxifen, trans reti‐ noic acid, thalidomide, ticlopidine, argatroban and strontium (89Sr) [Dispenzieri et al. 2007]. The effectiveness of these drugs is limited and further clinical trials are required.

Lenalidomide seems to be one of the most promising immunomodulatory drugs to treat PO‐ EMS syndrome, but further clinical studies are required [Dispenzieri et al. 2007].

High dose chemotherapy assisted auto-SCT remains the best therapeutic method, although it also has the highest mortality rate.
