Haematologica 2003 - Supplements

References
Effect of dose-intensive intravenous melphalan and autologous
blood stem-cell transplantation on AL amyloidosis associated
renal disease, Dember et al, Ann Intern Med 2001 May 1;134
(9pt1): 764-53
New aspect of treatment of nephrotic syndrome, Schwartrz.A, J
am Soc nephrol 2001, Feb;12 suppl17: s 44-7
Primary systemic amyloidosis, Gertz and al, Curr treat Options
Oncol 2002 Jun; (3): 261-71
Autologous stem cell transplantation for primary systemic
amyloidosis, Comenzo and al, Blood, 2002, Jun 15;99 (12):
4276-82
An overview of the use of high-dose melphalan with autologous
stem cell transplantation for the treatment of AL amyloidosis,
Sanchoroawala and al, BMT, 2001 Oct; 28(7):637-42
Eligibility for hematopoietic stem-cell transplantation for primary
systemic amyloidosis is a favorable prognostic factor for survival,
Dispenzieri A and al, JCO, 2001, jul 15;19(14):3350-6
Current role of thalidomid in cancer treatment, Thomas DA and
Kantarjaian HM, Curr Opin oncol 200;12(6):564-73
300
Remarkable Neurological Improvement of POEMS
Syndrome Associated Severe Paraproteinemic
Polyneuropathy Following High-Dose Melphalan
Therapy With Autologous Stem Cell Transplantation:
Report of Two Cases
M. Kropff, R. Kiefer, G. Bisping, W.E. Berdel, J. Kienast
Department of Medicine/Hematology and Oncology, and
Department of Neurology, University of Muenster, Muenster, FRG.
Tel: +49-251-8347590; Fax: +49-251-8347592; E-Mail: kropff@unimuenster.de
High-dose melphalan therapy with autologous peripheral blood
stem cell transplantation (PBSCT) has recently been reported to
improve neurological disability in patients with POEMS
syndrome and other immune-mediated neuropathies. We report
two additional patients with rapidly progressive paraproteinemic
polyneuropathy.
Patient 1 was a 38-year-old male with a 5 year history of
progressive proximal and distal weakness, distal sensory loss, and
areflexia, making him wheelchair-bound within two years. The
patient exhibited a IgG lambda monoclonal gammopathy of
undetermined significance. Concomitant hepatosplenomegaly and
endocrinopathy (hypothyroidism and hypogonadism) were
suggestive of POEMS syndrome. High-dose glucocorticoids,
plasmapheresis and immunoglobulins were ineffective but six
cycles of pulsed cyclophosphamide caused transient slowing of
progression, maintained with cyclosporin for 18 months but
followed again by rapid progression.
Patient 2 was a 41-year-old male with an 8 month history of a
rapidly deteriorating sensorimotor length-dependent
polyneuropathy progressing to proximal muscle groups with loss
of ambulation within few months. This patient had a small
monoclonal IgA-lambda gammopathy (8 g/L), 20 % bone
marrow infiltration with monotypic plasma cells,
hepatosplenomegaly and endocrinopathy, as well. In addition,
deep vein thrombosis (DVT) of the vena cava inferior led to
edema of the lower extremities requiring continuous
anticoagulation. Subsequent to initial plasmapheresis, this patient
received standard myeloma induction regimen of four cycles
anthracycline/pulsed dexamethasone with a paraprotein response
but with little effect on neurological disability.
In both patients, neurophysiology revealed a severe
demyelinating and axonal sensorimotor polyradiculoneuropathy.
Amyloidosis was excluded by appropriate staining of bone
marrow and rectum biopsies.
Both patients were treated with high-dose melphalan (200 mg/m²)
and PBSCT subsequent to an alkylating agent-based stem cell
mobilization with granulocyte colony-stimulating factor (G-CSF,
10 µg/kg/d). The procedure was well tolerated. Hematologic
recovery was timely and sustained. Applying the
EBMT/IBMTR/ABMTR criteria, response was partial in patient
1 and complete in patient 2. Clinically, both patients rapidly
improved in neurological function, regaining normal strength in
proximal muscle groups as well as remarkable improvement in
the hands. However, nerve conduction studies after one year
showed little change.
After more than one year of follow-up, patient 1 still requires a
wheelchair for longer distances due to persisting sensory ataxia
and paresis of distal leg muscles while his residual paraprotein
remained stable. Patient 2 is ambulatory with only residual
paresis of peroneal muscles despite reappearance of a serum
paraprotein on immunofixation (no monoclonal paraprotein on
routine serum electrophoresis).
The rapid clinical improvement in our two patients further
supports a potential role for high- dose melphalan chemotherapy
and autologous stem cell transplantation as rescue treatment for
patients with rapidly deteriorating severe paraproteinemic
neuropathy and possibly other immune-mediated
polyneuropathies. Procedure related risks seem not to be
increased in comparison with other myeloma patients.
10.5 Allogeneic transplants
301
Myeloablative versus reduced-intensity conditioning
followed by allogeneic stem cell transplantation in
multiple myeloma patients
Paolo Corradini*, Vittorio Montefusco*, Elena Rizzo*, Anna
Locasciulli^, Fabio Ciceri#, Raffaella Milani, Jacopo
Mariotti*, Lucia Farina*, Ignazio Majolino^
*Hematology & Bone Marrow Transplantation Unit, Istituto
Nazionale dei Tumori, Dipartimento Scienze Mediche - University
of Milano, Italy; ^Dept. of Hematology, Ospedale San Camillo
Roma; #Dept. of Hematology, Ospedate San Raffaele Milano -
Italy
Multiple myeloma (MM) is still an incurable disease and
allogeneic stem cell transplantation (allo-SCT) is a potentially
curative strategy. Nevertheless, despite the high rate of clinical
and molecular remissions, allo-SCT is still characterised by a
relevant transplant-related mortality (TRM), which significantly
S222