scholarly journals Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1124-1127 ◽  
Author(s):  
Sophie Archambeault ◽  
Nikki J. Flores ◽  
Ayami Yoshimi ◽  
Christian P. Kratz ◽  
Miriam Reising ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Allele Specific ◽  
Myelomonocytic Leukemia

AbstractJuvenile myelomonocytic leukemia is an aggressive and frequently lethal myeloproliferative disorder of childhood. Somatic mutations in NRAS, KRAS, or PTPN11 occur in 60% of cases. Monitoring disease status is difficult because of the lack of characteristic leukemic blasts at diagnosis. We designed a fluorescently based, allele-specific polymerase chain reaction assay called TaqMAMA to detect the most common RAS or PTPN11 mutations. We analyzed peripheral blood and/or bone marrow of 25 patients for levels of mutant alleles over time. Analysis of pre–hematopoietic stem-cell transplantation, samples revealed a broad distribution of the quantity of the mutant alleles. After hematopoietic stem-cell transplantation, the level of the mutant allele rose rapidly in patients who relapsed and correlated well with falling donor chimerism. Simultaneously analyzed peripheral blood and bone marrow samples demonstrate that blood can be monitored for residual disease. Importantly, these assays provide a sensitive strategy to evaluate molecular responses to new therapeutic strategies.

scholarly journals Feasibility and Outcome of Hematopoietic Stem Cell Transplantation Combined with Decitabine for Children with Juvenile Myelomonocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5869-5869
Author(s):  
Huaying Liu ◽  
Chunfu Li ◽  
Yuelin He
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia

Abstract Background Juvenile myelomonocytic leukemia(JMML) is a rare clonalmyelodysplastic/myeloproliferative disorder that occurs during infancy and early childhood with poor prognosis. Chemotherapy has not been found to be dffective, and Hematopoietic stem cell transplantation(HSCT) is currently the only curative treatment for JMML. Relapse and engraftment failure are the major causes of HSCT failure in JMML. Patients and method We report the outcomes of 4 patients with JMML who received HSCT combined with Decitabine between 2014-2015. Patient median age was 2 years(range,1-3years), and 3 were boys and 1 girl. Decitabine was given before and after the HSCT for one time(20mg/m2.d X 5d、10mg/m2 .d X 5d). Before HSCT, all the patients received mild chemotherapy(three or four course). The bone marrow evaluations of all the patients before HSCT were complete remission(CR). Two patients received human leukocyte antigen(HLA)-matched HSCT from unrelated donors, and two patients received haploidentical HSCT from parents followed by unrelated cord blood transplantation(UCB). Conditioning regimen of Unrelated donor-PBSCT was Busulfan+fludarabine+Thiotepa+Thymoglobuline, and the conditioning of haplo-HSCT was Busulfan+fludarabine+Cytarabine+Thymoglobuline. The number of nucleated cells of HLA-matched HSCT was 8×108/kg. The number of nucleated cells of Haplo-HSCT was 47.2×108/kg、61.26×108/kg , respectively, and the number of nucleated cells of UCB was 7.23×107/kg、9.4×107/kg, respectively. GVHD prophylaxis was based on post-transplant high-dose cyclophosphamide(PTCy, 50mg/kg on days +3 and +4) combined with mycophenolate plus cyclosporine A or tacrlimus. Results: The median follow-up was 21 months(range,11-27 months). The overall survival(OS) and the Disease free survival(DFS) both were 100%, All the patients got 100% engraftment(Unrelated-donor stem cell engrafted and Haploidentical-donor stem cell engrafted in 2 and 2 patients , respectively). None of the patients developed relaps, the bone marrow evaluations were complete remission(CR) after HSCT. The most common toxicities were infection with neutropenia(100%, n=4), The cumulative incidences of acute GVHD gradesII-III and CMV infection were 50% and 75% respectively. Conclusion: The combination of decitabine and HSCT shows encouraging results with highly effective and less toxicity for JMML. The futhuer study should be developed in the future. Disclosures No relevant conflicts of interest to declare.

Rapid Cyclosporine Tapering and Isotretinoin Usage after Unrelated Donor Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5188-5188
Author(s):  
Keon Hee Yoo ◽  
Soo Hyun Lee ◽  
Ki Woong Sung ◽  
Hong Hoe Koo ◽  
Hye Lim Jung
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Differentiating Agent ◽  
Myelomonocytic Leukemia ◽  
Disease Free

Abstract Juvenile myelomonocytic leukemia (JMML) is a rare type of childhood leukemias, and allogeneic hematopoietic stem cell transplantation (HSCT) is known to be the only way to cure the disease. Unfortunately, relapse is still the most frequent cause of treatment failure after transplant in JMML. We investigated the feasibility of inducing graft versus leukemia (GVL) effect and the use of a differentiating agent even after unrelated HSCT in children with JMML. Seven consecutive patients with JMML underwent unrelated HSCT at a median age of 17 months. The sources of grafts were bone marrows (n=3) or HLA 1- or 2-antigen mismatched cord bloods (n=4). Only 3 of the 7 patients were in complete remission before transplantation. Intravenous busulfan, cyclophosphamide, and etoposide were used as preparative agents except in one who was conditioned with TBI-based regimen. Cyclosporine was used universally for GVHD prophylaxis with additional use of short-term methotrexate in bone marrow transplants and of methyl-prednisolone in cord blood transplants. Cyclosporine was tapered rapidly from around 1 month post-HSCT and isotretinoin (75–100 mg/m2/day) was used in selected patients who have any risk factors of relapse. Cyclosporine blood levels were 247.8±91.1, 146.6±104.2, and 88.8±52.6 ng/mL at 1, 2, and 3 months post-transplant, respectively. There was no grade 3 or 4 acute GVHD and only 2 patients developed grade 2 acute GVHD which was improved without additional treatment. Chronic GVHD was developed in 3 (1 limited, 2 extensive) of the evaluable 5 patents, which was all resolved after combined use of immune suppressive agents. Initial chimeric status analysis at 1 month revealed complete donor chimerism (CC) in 4 patients, mixed chimerism (MC) in 2 and autologous recovery (AR) in one. One of the patients with MC and the one with AR were in disease-free status. One patient whose chimeric status changed from CC to MC eventually relapsed. One patient with initial MC with residual disease turned to CC with complete remission. Another patient with initial MC but with no evidence of disease is on treatment with isotretinoin without relapse for 3 months even with persistent MC. The patient with AR relapsed early after transplant. Five patients are alive relapse-free and disease-free with a median follow-up of 16 months after transplant. The Kaplan-Meier probability of event-free survival was 66.7%. We suggest that GVL induction strategy with concomittant use of a differentiating agent might have a role to suppress leukemic relapse in JMML.

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