Granulocytic sarcoma is a localized tumor composed of immature cells of the granulocytic series. Most granulocytic sarcomas occur in the course of acute leukemia and the blast crisis of chronic leukemia. Rarely, however, it may present before leukemia becomes clinically apparent. It may also occur in patients with myeloproliferative disorders. It has been reported that it occurs in 3% to 9% of patients with acute myelogenous leukemia (AML) and the incidence of granulocytic sarcoma is reported to be higher in patients with t (8;21). However, epidural granulocytic sarcoma associated with t (8;21) is very rare. In this report, we describe a patient with AML associated with t (8;21) in whom the cord compression occurred due to epidural granulocytic sarcoma. In addition, this case present infiltration of both pleura by blast cells. She was treated with local irradiation and chemotherapy successfully.
Blast Crisis ; Drug Therapy ; Humans ; Incidence ; Leukemia ; Leukemia, Myeloid, Acute* ; Myeloproliferative Disorders ; Pleura ; Sarcoma, Myeloid* ; Spine* ; Sternum*

Adult ; Benzamides ; Blast Crisis ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; pathology ; Male ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

Adult ; Antibiotics, Antineoplastic ; therapeutic use ; Benzamides ; Blast Crisis ; drug therapy ; Drug Resistance, Neoplasm ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; Sirolimus ; therapeutic use

OBJECTIVETo investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).

METHODSThe clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.

RESULTSIn 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.

CONCLUSIONT315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.

Acute Disease ; Blast Crisis ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Protein Kinase Inhibitors ; therapeutic use

OBJECTIVESTo evaluate the efficacy and safety of imatinib mesylate (imatinib) for patients with Philadelphia chromosome-positive (Ph+ ) chronic myeloid leukemia (CML) in accelerated and blastic phase.

METHODSSeventy-five Ph+ CML patients in accelerated phase and 49 in blastic phase were treated with 400 mg or 600 mg of imatinib once daily.

RESULTSFor patients in accelerated phase, the cumulative hematological response (HR) rate was 93.3%, including complete HR (CHR) rate 85.3%, and returning to chronic phase (RCP) rate 8% in a median follow-up of 23.0 (1.0 -64.0 ) months. Cumulative major cytogenetic response (MCyR) rate was 33.0%, and complete cytogenetic response (CCyR) rate 28.0%. For patients with CCyR, the major molecular response (MMoR) rate was 47.6%. The estimated 4-year progression-free survival (PFS) rate and overall survival (OS) rate were 48.2% and 52.2% in patients with HR, respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 37.3%, 34.6% and 45.3% of all patients, respectively. For patients in blastic phase, the cumulative HR rate was 63.3%, including CHR rate 44.9%, and RCP rate 18.4% in a median follow-up of 4.5 (0.3 -63.0) months. Cumulative MCyR rate and CCyR rate were both 12.2%. For patients with CCyR, the MMoR rate was 33.3%. For patients with HR, the estimated 1-year/2-year PFS and OS rates were 32.8%/15.8% and 46.0%/ 21.0% respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 75.5%, 71.4% and 73.5% of all patients, respectively.

CONCLUSIONSThe efficiency of imatinib was decreasing, and severer hematological toxicities increasing with the disease progressing in patients with Ph+ CML. Imatinib improves progression-free survival significantly in most patients in accelerated phase, particularly in those with continuous CCyR or MMoR. The response duration in majority of blastic phase patients is short, and the relapse rate is high.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Blast Crisis ; drug therapy ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Accelerated Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the efficiency of dasatinib as the second- or third-line tyrosine kinase inhibitor (TKI)in imatinib-resistant patients with chronic myeloid leukemia (CML)based on BCR-ABL mutation detection.

METHODS122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib- and nilotinib-resistance, 55 in the chronic-phase (CP), 21 in the accelerated- phase (AP)and 46 in the blast- phase (BP). Those harboring dasatinib highly- resistant mutations (T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival (PFS)and overall survival (OS)were analyzed. BCR- ABL mutation detection was performed once the patients failed on dasatinib.

RESULTSIn the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR)and molecular response 4.5 (MR4.5)were 92.7%, 53.7%, 29.6% and 14.8%, respectively. 4-year PFS and OS rates were 84.4% and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0% and 35.0%; and 3-year PFS and OS rates were 56.1% and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0% and 21.4%; and 1-year PFS and OS rates were 43.6% and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second- line TKI or the third-line TKI. Of the 75 patients who were resistant to dasatinib, 37 (48.7%)developed new mutation(s), and T315I (59.5%)was the most common mutation type. The patients who already harbored mutation(s)before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib (65.7%vs 34.1%,P=0.006).

CONCLUSIONSDasatinib was proved to be effective in the treatment of imatinib- or/and nilotinib-resistant CML patients, especially in both CP and AP cohorts. The significance of BCR-ABL mutation screening and monitoring should be highlighted before and during dasatinib therapy.

Blast Crisis ; Cytogenetics ; Dasatinib ; therapeutic use ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines

The t(3;21) (q26;q22) is associated with chronic myelogenous leukemia in blast crisis, leukemia evolving from therapy-related myelodysplasia, and with leukemia following other hematopoietic proliferative diseases. The t(3;21) is rare secondary aberration in blast crisis of Philadelphia(Ph)-positive chronic myeloid leukemia, which may be restricted to patients entering myeloid blast crisis. We report here in one case of chronic myeloid leukemia in blast crisis which reveals both t(9;22) (q34;q11), and t(3;21) (q26 ;q22). A 62-year-old male was diagnosed as chronic myeloid leukemia 5 years ago, received hydroxyurea therapy, and admitted because of gingival bleeding and fever. On examination, splenomegaly and leukocytosis with proliferated blasts(91%) in peripheral blood were noted. Bone marrow aspirate showed hypercellularity with severe blast proliferation(92.5%) which revealed all negative in peroxidase and PAS stain. Cytogenetic study of bone marrow cells showed the karyotype 46, XY, t(3;21) (q26;q22), t(9;22) (q34;q11), which might be suspected as myeloid blast crisis. Above finding was confirmed by the result of immunophenotyping(CD13 43.6%, CD34 68.2%, HLA-DR 91.6%). He received intensive chemotherapy, but still sustained proliferation of blasts was noted . The follow up cytogenetic study was as follows: 46, XY, 4(3;21) (q26:22), t(9;22) (q34;q11)/46, XY, t(3;21)(q26;q22), del(8) (q22), t(9:22) (q34,q11)/46, XY (16/3/1). He died soon from severe pancytopenia and sepsis.
Blast Crisis* ; Bone Marrow ; Bone Marrow Cells ; Cytogenetics ; Drug Therapy ; Fever ; Follow-Up Studies ; Hemorrhage ; HLA-DR Antigens ; Humans ; Hydroxyurea ; Karyotype ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Leukocytosis ; Male ; Middle Aged ; Pancytopenia ; Peroxidase ; Sepsis ; Splenomegaly

Granulocytic sarcoma is an uncommon tumor composed of immature cells of the granulocytic series, occurring in patients with acute myelogenous leukemia and blast crisis of chronic myelogenous leukemia. It may be rarely preceded by an acute myelogenous leukemia and follows an unformly fatal course. We report a case of granulocytic sarcoma of extradural space presenting as the spinal cord compression without any evidence of leukemia in the peripheral blood. The tumor was located extraduraly in the C6-C7 area compressing the dural sac and spinal cord. After left hemilaminectomy of C6 and C7, this mass was removed completely. Postoperatively, symptoms and signs were improved. At the postoperative 10th day, the patient lost consciousness and peripheral blood study showed the findings of acute myelogenous leukemia. Thereafter, the patient received chemotherapy with Ara-C and Daunorubicin, but hematologic remission was not obtained completely. After 4 months, he revisited our hospital owing to fever, and the septic shock was encountered. The patient died of sepsis.
Blast Crisis ; Consciousness ; Cytarabine ; Daunorubicin ; Drug Therapy ; Fever ; Humans ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Sarcoma, Myeloid* ; Sepsis ; Shock, Septic ; Spinal Cord ; Spinal Cord Compression ; Spine*

Tumor lysis syndrome (TLS) defines the metabolic derangements that occur with tumor breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular materials and their metabolites into the extracellular space. The syndrome causes hyperuricemia, hyperkalemia, hyperphosphatemia, secondary hypocalcemia and uremia. It can result in acute renal failure and be fatal. Early recognition of patient at risk and preventive measures are important. There is a high incidence of TLS in tumors with high proliferative rates and large burden such as acute lymphoblastic leukemia and Burkitt's lymphoma. It less commonly occurs in solid tumors such as testicular cancer, breast cancer and small cell lung cancer. There are only a few reports on TLS complicated in CML in blast crisis. So we report a 45-yr-old woman presenting with TLS associated with CML in lymphoblastic crisis after the initiation of cytotoxic chemotherapy.
Acute Kidney Injury ; Blast Crisis ; Breast Neoplasms ; Burkitt Lymphoma ; Drug Therapy ; Extracellular Space ; Female ; Humans ; Hyperkalemia ; Hyperphosphatemia ; Hyperuricemia ; Hypocalcemia ; Incidence ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Small Cell Lung Carcinoma ; Testicular Neoplasms ; Tumor Lysis Syndrome* ; Uremia

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.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome