Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP).@*METHODS@#The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test.@*RESULTS@#A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group.@*CONCLUSION@#The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.

Advances in the treatment for blast phase myeloproliferative neoplasm / 中国肿瘤临床

Blast phase myeloproliferative neoplasm (MPN-BP) represent a type of secondary acute leukemia and are associated with a poor patient prognosis worldwide. Currently, there is no standardized treatment regimen for MPN-BPs, and treatment remains a major clinical challenge. In recent years, significant progress has been made in understanding the biological mechanisms of MPNs, especially the abnormal activation of the JAK-STAT signaling pathway caused by driver gene mutations; this has opened up a new avenue in exploring the mechanism and treatment of MPN-BP. However, in terms of disease pathogenesis, MPN-BP are different from primary acute leukemia, and different therapeutic strategies for MPN-BP have also been investigated. This article focuses on the advances made in MPN-BP treatment.

Chronic myeloid leukemia with blast phase as initial manifestation: report of three cases and analysis of laboratory characteristics / 白血病·淋巴瘤

Objective@#To explore the clinical and laboratory features of chronic myeloid leukemia(CML) patients with blast phase as initial presentation.@*Methods@#The clinical manifestation, laboratory bindings and treatment of 3 CML patients with blast phase as the initial presentation from January 2015 to November 2016 in Luoyang Central Hospital Affiliated to Zhengzhou University were analyzed. The first symptoms of 3 patients were similar to acute leukemia.@*Results@#The patients were presented with splenomegaly, obvious rise of white blood cell count in peripheral blood, increasing number of initial cells in the bone marrow, Philadelphia chromosome-positive (Ph+), fluorescence in situ hybridization of bcr-abl1 with fusion signals in segmented granulocytes, fusion gene with p210 positive and without the typical chronic phase of CML.@*Conclusions@#Due to the increased number of marrow blasts and the similarity of clinical manifestations to acute leukemia in CML patients with blast phase as the initial presentation, it is easy to misdiagnose as Ph+ acute leukemia in the initial phase. While some differences in genetics, clinical manifestations and genomics between them may help in differential diagnosis.

A case of chronic myeloid leukaemia in blast transformation with leukemic ascites

Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.

The Cytologic Features of Chronic Myelogenous Leukemia and Its Lymphoid Blast Phase in Body Fluid: A Case Report

Although chronic myelogenous leukemia (CML) may be involved in any part of the body, infiltration of the body fluid has rarely reported in the literature. Here we report on a 35 year-old male patient who was diagnosed chronic myelogenous leukemia ten years previously and he received allogenic hematopoietic stem cell transplantation. He then presented with left knee pain eight years after the initial diagnosis. MRI revealed a soft tissue mass at the distal femur. Cytology of the joint fluid revealed myeloblasts, promyelocytes, eosinophilic myelocytes, band neutrophils, megakaryocytes and orthochromatic erythroblasts, which was all consistent with leukemic infiltration of the knee joint fluid. The immunohistochemistry was positive for CD34, CD117 and myeloperoxidase (MPO). Despite that the patient underwent radiation therapy, MRI revealed growth of the mass, and ten months later, the lymphoid blast phase of CML was confirmed after biopsy. The patient received an above knee amputation. Five months later, multiple masses were revealed on PET-CT at the left iliopsoas muscle, abdominal wall and bones. Bilateral pleural effusion occurred shortly after this. Cytologic evaluation of the pleural fluid also revealed blast-like cells, and histologic evaluation of the abdominal mass confirmed the lymphoid blast phase of CML with positivity for CD3, UCHL-1, CD34 and CD117, but negativity for MPO.

Mutation of the N-ras Gene in a Patient Suffering from the Blast Phase of Chronic Myelogenous Leukemia

The blast phase in chronic myelogenous leukemia (CML) is associated with mutation of several genes. It is well known that p53 gene mutation plays a key role in the myeloid or lymphoid blast phase of CML. But for the case of the N-ras gene, the association between N-ras mutations and the blast phase of CML is not yet known. We report here on a case of detecting N-ras point mutation without p53 mutation in a 64 year-old man who suffered from the lymphoblastic blast phase of CML.