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Updated: Sep 27, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of
Sara Galimberti1, Fortunato Morabito, Francesca Guerrini
1Department of Oncology, Transplant and Advances in Medicine, Section of Haematology, University of Pisa, Italy.
Abstract:
To evaluate the clinical impact of minimal residual disease in multiple myeloma, apheretic products from 51 autotransplanted patients were tested by fluorescent (GeneScan) polymerase chain reaction (PCR). Sixty-nine per cent of harvests were contaminated when evaluated for IgH rearrangement. Forty-six patients responded to transplant, with 52.9% achieving complete response (CR). The clinical response of patients was significantly influenced by the number of re-infused CD34+ cells. Positive PCR results of re-infused harvests were not significantly related to patient outcome. Median overall survival (OS) was 33 months, and a significant advantage for patients transplanted by 12 months from diagnosis was observed. Moreover, OS was longer for patients receiving PCR-negative stem cells, with 72% of patients surviving to 70 months in the group receiving PCR-negative harvests vs 48% in the group transplanted with contaminated precursors (not statistically significant). Ex vivo purging caused a reduction of contamination of up to 3 logs; nevertheless, 80% of purged harvests remained PCR-positive and the purging procedure did not alter response or survival rates. Thus, the failure of a predictive role for this highly sensitive molecular method could be explained by the assumption that in vivo persisting malignant cells are the true source of relapse in MM.
Insights
Minimal residual disease in multiple myeloma (MM) stem cell harvests was assessed. While PCR detection of IgH rearrangement in harvests did not predict patient outcomes, PCR-negative stem cells correlated with longer survival in MM patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Minimal residual disease (MRD) is a critical factor in multiple myeloma (MM) prognosis.
- Assessing MRD in autologous stem cell harvests is crucial for understanding transplant efficacy.
Purpose of the Study:
- To evaluate the clinical impact of MRD in MM using polymerase chain reaction (PCR) on apheresis products.
- To determine if MRD detection in stem cell harvests predicts patient response and survival after autotransplantation.
Main Methods:
- Analysis of apheresis products from 51 autotransplanted MM patients for IgH rearrangement using fluorescent (GeneScan) PCR.
- Correlation of PCR results with patient response, CD34+ cell dose, and overall survival (OS).
- Evaluation of ex vivo purging efficacy on MRD reduction and its impact on outcomes.
Main Results:
- Sixty-nine percent of harvests showed IgH rearrangement contamination.
- Patient response was significantly influenced by re-infused CD34+ cell count.
- PCR positivity in harvests did not significantly correlate with patient outcomes.
- Median OS was 33 months; earlier transplant (within 12 months) improved survival.
- Patients receiving PCR-negative stem cells had longer OS (72% at 70 months) compared to those with PCR-positive harvests (48%), though not statistically significant.
- Ex vivo purging reduced contamination but 80% of purged harvests remained PCR-positive, without improving response or survival rates.
Conclusions:
- The presence of MRD in stem cell harvests, detected by PCR, may not be the sole determinant of relapse in MM.
- In vivo residual disease might be the primary driver of relapse, irrespective of harvest contamination.
- Further research is needed to elucidate the precise role of MRD in MM post-transplant outcomes.
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