Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia.
We present five cases of concomitant relapsed multiple myeloma and therapy related myelodysplasia (t-MDS). After treatment with thalidomide marked anti-myeloma activity was observed, but it was associated with rapid progression of the MDS clone to acute myeloid leukemia (AML). This paradoxical effect of thalidomide is concerning because there is increasing use of thalidomide in relapsed, heavily treated multiple myeloma patients who already have a higher propensity to develop MDS. The leukemic transformation in our cases most probably reflects the natural progression of MDS, though it clearly demonstrates that thalidomide is ineffective in controlling blast proliferation in t-MDS. More concerning, however, is the possibility that thalidomide, while suppressing the myeloma clone, eliminates inhibitory signals and subsequently stimulates the proliferation of the leukemic clone. The use of thalidomide should be carefully assessed in relapsed multiple myeloma patients with clinical and cytogenetic evidence of t-MDS.
Badros
Ashraf
A
Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, USA. abadros@umm.edu
Morris
Christopher
C
Zangari
Maurizio
M
Barlogie
Bart
B
Tricot
Guido
G
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D036102:Peripheral Blood Stem Cell Transplantation; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D013792:Thalidomide; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin