Isotype class switching after transplantation in multiple myeloma.

2nd Department of Medicine-Department of Clinical Haematology, Charles University Teaching Hospital, Králové, Czech Republic.
Neoplasma (Impact Factor: 1.57). 02/2007; 54(3):225-8.
Source: PubMed

ABSTRACT Switching of the paraprotein isotype or transient presence of oligoclonal bands detectable by serum immunofixation electrophoresis has been reported following not only transplantations, but also after intensive chemotherapy for leukemia. Retrospective analysis of 72 transplanted myeloma patients was carried out to determine the frequency and clinical significance of the appearance of abnormal proteins bands (APB) distinct from the original paraprotein. APB presence was observed in 31 patients (43%) already after the first autotransplant, the median interval from transplant was 2 months (range, 1 to 6 months). The most frequent occurrence of APB was observed after allogeneic transplantation. In the group of patients with APB presence more patients achieved complete remission (32.2% versus 17.1%), statistically significant differences were also established when we compared the percentage of surviving patients and overall survival, to the present date, among both groups of patients (p=0.03). All relapsed patients with previous isotype class switching had disease characterized by the same type of paraprotein as that detected at diagnosis. The development of APB is likely related to the recovery of impaired immunoglobulin production after transplantation. We confirmed favourable prognostic significance of this finding in transplanted myeloma patients.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.
    Cancer Immunology and Immunotherapy 02/2012; 61(10):1639-51. · 3.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Paraproteinaemia following allo-SCT is common. We analysed 91 consecutive patients undergoing allo-SCT; conditioning included alemtuzumab in 42% of the patients. Paraproteinaemia incidence at 2 years was 32%. In univariate analysis paraproteinaemia was associated with unrelated donor, age, recipient seropositivity for CMV and alemtuzumab conditioning (hazard ratio (HR) 3.93, P=0.0006). Paraproteinaemia was not associated with haematological diagnosis; disease status at transplant; varicella zoster, herpes simplex or EBV serology; reduced-intensity vs myeloablative conditioning or GVHD. CMV reactivation-more frequent in alemtuzumab recipients-was associated with paraproteinaemia (HR 7.52, P<0.0001). In multivariate analysis, only increasing age (HR 1.04 per year, P=0.048) and CMV reactivation (HR 5.74, P=0.001) were significantly associated with paraproteinaemia. Alemtuzumab without CMV reactivation, however, resulted in significantly more paraproteinaemia, suggesting an effect that is independent of CMV reactivation. OS was poorer in patients with paraproteinaemia (HR 2.54, P=0.04) and relapse increased (HR 2.38, P=0.087). Paraproteinaemia was not significantly independently associated with decreased survival on multivariate analysis. Post transplant paraproteinaemia is associated with CMV reactivation, is more frequent in alemtuzumab-conditioned transplants and is not associated with improved OS.
    Bone marrow transplantation 10/2010; 46(7):993-9. · 3.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasma cell myeloma, characterized by clonally aberrant plasma cells that produce abnormal monoclonal Igs, is the most common indication for autologous hematopoietic progenitor cell transplantation (AHPCT) in North America. We observed appearance of new monoclonal gammopathies different from the original protein in the post-AHPCT setting and termed this condition 'secondary MGUS' (monoclonal gammopathy of undetermined significance). Hence, we performed a retrospective, single institution review of serum protein electrophoresis/immunofixation electrophoresis data in 92 AHPCT recipients from the period 2000-2009. In all, 22 of 92 patients (24%) undergoing AHPCT met criteria for secondary MGUS. Contrary to previous studies, often referred to as 'abnormal protein banding,' we did not observe this condition as a favorable prognostic indicator in affected patients when compared with the control group (P=0.686). However, we did note that a subgroup of the study cohort who developed secondary MGUS after a prolonged latency (>10 months) had an improved median OS compared with the remainder of the study cohort (75 months vs 41 months, P=0.005). As there have been significant advancements in understanding the pathobiology and clinical significance of MGUS, we believe that secondary MGUS merits dedication of resources for investigation to determine its true clinical relevance, prognostic value and pathophysiology.
    Bone marrow transplantation 12/2011; 47(9):1212-6. · 3.00 Impact Factor