scholarly journals Evading Capture by Residual Disease Monitoring: Extramedullary Manifestation ofJAK2V617F-Positive Primary Myelofibrosis After Allogeneic Stem Cell Transplantation

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Stephen E. Langabeer ◽  
James Nolan ◽  
Karl Haslam ◽  
Lindsey Clarke ◽  
Richard Flavin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Residual Disease ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Clinical Intervention ◽  
Primary Myelofibrosis ◽  
Disease Monitoring

Monitoring of theJAK2V617F allele burden in myeloproliferative neoplasms after allogeneic stem cell transplantation is useful to determine levels of residual disease and has the potential to detect early relapse and guide subsequent clinical intervention. A case is described of aJAK2V617F-positive primary myelofibrosis patient who underwent allogeneic stem cell transplantation. Prospective residual disease monitoring of the peripheral blood failed to detect an extramedullary manifestation of the disease, a periorbital myeloid sarcoma, arising nearly three years after transplant. This case serves to highlight a pitfall in residual disease monitoring for myeloproliferative neoplasm-associated mutations in the post-allogeneic stem cell transplantation setting.

Is Splenectomy Necessary in Patients with Myelofibrosis and Extensive Splenomegaly Prior to Allogeneic Stem Cell Transplantation with Reduced Intensity Conditioning Regimens?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1091-1091
Author(s):  
Stefan O. Ciurea ◽  
Barry Sadegi ◽  
Andrew Wilbur ◽  
Victoria Alagiozian-Angelova ◽  
Sujata Gaitonde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Significant Risk ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
Marrow Fibrosis

Abstract Allogeneic stem cell transplantation has been shown to restore normal hematopoiesis in patients with intermediate or high risk primary myelofibrosis (PMF) or myelofibrosis preceeded by polycythemia vera or essential thrombocythemia. However, in patients with PMF and extensive splenomegaly it is not clear whether transplant is associated with an unacceptable risk or if splenectomy should be performed prior to transplant. In this study, ten consecutive patients with myelofibrosis who were not splenectomized received an allogeneic hematopoietic stem cell transplantation (HSCT) from related or unrelated donors and were periodically monitored by ultrasound or CT scan for 12 months after transplant to assess the kinetics of the reduction of splenomegaly. These findings were correlated with the time to resolution of marrow fibrosis, time to engraftment and clinical outcome. Over a 12 month period a progressive reduction in spleen size was observed in all the patients and paralleled the reduction in marrow fibrosis (Figure 1). Of 10 patients, 5 with a splenic longitudinal diameter >30 cm showed a more prolonged time to engraftment ANC> 0.5 × 109/L (d 19±5 vs 13±2, p=0.05) and platelet > 20 × 109/L (d 75±104 vs 11±2, p=0.06). However, of the 5 patients with more extensive splenomegaly only 2 experienced delayed engraftment of platelets (d 77 and 256, respectively). Full donor chimerism was observed in all patients within 60 days after transplantation regardless of the size of the spleen. At a median follow-up of 54 months (range: 2–80) all the patients are alive but 1 who died of a TTP like syndrome 2 months after transplant and had a small spleen at the time of transplant. A clinical CR has been documented in 7 patients and 2 have achieved clinical improvement as assessed by IWG response criteria. These findings suggest that allogeneic HSCT with RIC regimen can be safely performed in patients with extensive splenomegaly. Although in these patients the time to engraftment may be prolonged, the significant risk of morbidity and mortality associated with splenectomy may be avoided. Figure Figure

Monitoring of Donor Chimerism in CD34+ Peripheral Blood Progenitors Allows to Detect Minimal Residual Disease after Allogeneic Stem Cell Transplantation -Results of a Randomized Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 340-340
Author(s):  
Martin Bornhaeuser ◽  
Uta Oelschlaegel ◽  
Gesine Bug ◽  
Uwe Platzbecker ◽  
Karin Lutterbeck ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Preemptive Therapy ◽  
Study Group ◽  
Minimal Residual

Abstract Relapse of hematological malignancy remains a major complication after allogeneic stem cell transplantation. This is especially true for patients receiving minimal or reduced-intensity conditioning therapy. Analysis of donor chimerism (DC) is an important diagnostic tool to assess the risk of relapse after allogeneic stem cell transplantation, especially in patients lacking a specific marker suitable for monitoring of minimal residual disease. The sensitivity of a standard PCR assay amplifying short-tandem-repeat sequences can be improved significantly by investigating sorted CD34+ peripheral blood cells. We prospectively compared the serial analysis of DC in selected CD34+ cells and unmanipulated whole blood (WB) within a randomised study in 131 patients with CD34+ hematological malignancies (AML, ALL and MDS) surviving more than 100 days after transplantation. The primary end-point was the association between decreasing CD34+ DC and haematological relapse. Whenever a decreasing CD34+ or WB DC was confirmed and no signs of active GvHD were present, a rapid taper of CsA or tracolimus (50% every 5–7 days) was suggested. If no GvHD occurred within 14 days after the stop of CsA or tacolimus, patients were scheduled to receive donor lymphocyte infusions (DLI) in incremental doses. The cumulative incidence of relapse was significantly increased in patients with decreasing or incomplete CD34+ DC (62% vs. 38%, p=0.01). This was associated with a lower probability of overall survival (20% vs. 39%, p=0.03). The interval between the decrease in CD34+ DC and hematological relapse was 35 days (range 0–567) in the study group compared to only 8 days (range 0–63) in the control group monitored by WB DC analysis (p=0.05). The median time between a decrease in CD34+ DC and WB DC was 14 days (range, 0 to 445). Patients receiving preemptive therapy triggered by decreasing CD34+ DC had a significantly higher probability of disease-free survival compared to cases monitored and treated according to WB DC (19% vs. 0%, p=0.009). Multivariate analysis revealed age, disease-risk and decreasing CD34+ DC as independent risk-factors for overall survival in the study group. In summary, we could demonstrate that the quantification of DC in CD34+ selected cells is a sensitive method to predict relapse and survival after allogeneic SCT. Although this technology opens a window for preemptive therapy, new treatment approaches have to be employed to improve the overall outcome of patients with recurrence of residual disease after allogeneic stem cell transplantation.

Allogeneic Stem Cell Transplantation In Philadelphia Negative Myeloproliferative Or Myelodysplastic/Myeloproliferative Neoplasms: A Retrospective Analysis From The Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3373-3373
Author(s):  
Xavier Cahu ◽  
Patrice Chevallier ◽  
Aline Clavert ◽  
Felipe Suarez ◽  
Mauricette Michallet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Disease ◽  
Myeloproliferative Neoplasms ◽  
Thrombotic Event ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Blast Phase

Abstract Background Philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasms may evolve towards secondary acute myeloid leukemia (AML). The prognosis of such secondary leukemia is very poor. At present, there are only a few reports assessing the outcome of adult patients with a philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasm in blast phase (MPN-BP) who received allogeneic stem cell transplantation (allo-SCT). Patients and Methods in this retrospective study, inclusion criteria were: (i) adult patients with a MPN-BP (ii) who received first allo-SCT (iii) between 2000 and 2010 (iv) irrespective of the stem cell source or conditioning regimen. MPN with <20% blasts in blood/bone marrow and AML secondary to myelodysplastic syndromes were excluded from this analysis. Results 60 patients were included. MPN, AML and allo-SCT characteristics are described in table 1. Median age at allo-SCT was 57 (range, 30-68). Patients received allo-SCT in first complete remission (CR1), CR2 or in advanced disease in 22 (37%), 4 (7%) and 34(57%) of cases, respectively. Engraftment was achieved in 55 cases (92%). With a median follow-up of 31 months (range, 25-44), the 3-year overall survival (OS) and Leukemia-Free-Survival (LFS) were respectively 18% and 9%. The 3-year transplant-related mortality (TRM) was 24% whereas relapse incidence was 68%. The 3-year LFS of patients grafted in CR (n=26) was 18% whereas the 3-year LFS of patients allografted in advanced disease (n=34) was only 3% (p=0.008). In the CR group, the 3-year TRM was 24% whereas relapse incidence was 61%. Intermediate or good AML karyotype (3-year LFS of 33% versus 10% for adverse AML karyotype, p=0.03) and the absence of a previous thrombotic event (3-year LFS of 24% versus 0, p=0.02) were associated with an improved LFS in patients allografted in CR. Conclusion These results suggest that the outcome of patients with a MPN-BP is dismal despite allo-SCT due to a high relapse incidence even in patients transplanted in CR. Outside a clinical trial, allo-SCT should be mainly proposed to patients in CR. New strategies are mandatory to improve the outcome of patients in blast phase. Disclosures: No relevant conflicts of interest to declare.

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