Hypercvad Plus Imatinib or Dasatinib for Patients with Lymphoid Blastic Phase of Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3766-3766
Author(s):  
Paolo Strati ◽  
Hagop M. Kantarjian ◽  
Deborah A. Thomas ◽  
Susan M. O'Brien ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Chronic Phase ◽  
Transcript Levels ◽  
Advanced Phase ◽  
Blastic Phase ◽  
Starting Dose

Abstract Abstract 3766 Background: Chronic Myeloid Leukemia (CML) may progress at advanced phase at the rate of 1–1.5% per year. Blastic phase (BP) CML (defined by a bone marrow blast count >30%) can show lymphoid features in up to 20–30% of cases. With the use of single agent imatinib or dasatinib, median overall survival (OS) ranges between 7 and 11 months. Combination therapy may offer an improved outcome. We analyzed the outcome of patients (pts) with lymphoid BP-CML treated with hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone (HCVAD) plus imatinib or dasatinib. Methods: 32 pts with lymphoid BP-CML were treated at MD Anderson with HCVAD plus imatinib or dasatinib between 2000 and 2011. The starting dose of imatinib was 400 mg (2 pts), 600 mg (20 pts) and 800 mg (1 pt). The starting dose of dasatinib was 50 mg (1 pt), 100 mg (7 pts) and 140 mg (1 pt). Survival curves were calculated using Kaplan-Meier estimates and were compared using the log-rank test. Results: the median age was 48 (22–74) and 72% were male. Four (12%) pts had a de novo diagnosis, 21 (66%) were previously treated with a tyrosine kinase inhibitor (TKI) for chronic phase (CP) and 3 (9%) for BP. At diagnosis, median WBC was 23.4 (1.1–165.4) x109/L, hemoglobin 10.6 (6.3–16.4) g/dL, platelets 51 (6–526) x109/L, blasts 33 (0–91)%, basophils 0 (0–2)%, creatinine 1 (0.6–1.5) mg/dL, albumin 3.8 (2–4.7) g/dL, bilirubin 0.5 (0.2–3.4) mg/dL, alanine aminotransferase 34 (12–446) IU/L; on bone marrow, median blasts were 78 (26–97)%, basophils 0 (0–4)% and additional chromosomal aberrations (ACA) were found in 15/24 (62%) pts, affecting mostly chromosome (chr) 7 (60%), chr9 (40%), chr8 (33%) and chr1 (27%). Before BP diagnosis, median Philadelphia (Ph) positivity by FISH was 67% (0–96); 6/14 (43%) pts showed a Ph mutation (Y253H, T315I, Q252H, F317L, E255K, M244V) at time of progression to BP. Median time from CML diagnosis to BP was 18 (2–33) months, with no significant differences according to previous Ph FISH positivity or CML therapies. Imatinib was added to HCVAD in 23 pts and Dasatinib in 9. Complete Remission (CR) was obtained in 27 (84%) of them (78% with imatinib, 100% with dasatinib). Twenty-three of 27 (87%) CR were achieved after 1stcycle of induction. Early mortality (i.e., within 60 days) occurred in 3 pts. Patients received a median of 4 (1–8) cycles of HCVAD. At the time of CR, median BCR-ABL transcript levels were 1.7 (0–100). The levels decreased to a median of 0.01 (0–100) after 3–4 cycles of therapy; 7/27 (26%) pts achieved negative values of BCR-ABL transcripts after a median of 2 (1–4) months. Three (43%) of 7 pts who achieved complete molecular remission relapsed. MRD by flow cytometry became negative in 15/17 (88%) pts: 14 after induction, 1 after 2 months. Six (40%) of the pts with negative flow cytometry for MRD relapsed. Thirteen pts received SCT in remission: 4 relapsed and died after SCT. Median Progression Free Survival (PFS) was not reached and was longer among SCT recipients (p=0.03) and patients who had a negative flow cytometry at the time of CR (p<0.001). OS was 17 (7–27) months and was longer in patients with no more than 1 line of treatment for CP of CML, with ACA (p=0.01) and among SCT recipients (p<0.001). Among patients who had a CR, OS was longer if flow cytometry was negative at the time of CR (p=0.02) and if BCR-ABL transcript levels were < 1.7% (p=0.01) at the time of CR or <0.025% as best result (p=0.03). Conclusions: HCVAD plus imatinib or dasatinib is an effective regimen for pts with lymphoid BP CML, particularly when followed by SCT. ACA and less than 1 treatment for CML are positive prognostic factors. Better results are observed if negative flow cytometry and low levels of BCR-ABL transcripts are achieved with therapy. Disclosures: Ravandi: BMS: Honoraria, Research Funding.

Significant Discrepancy In Peripheral Blood Compared to Bone Marrow BCR-ABL Transcript Levels In Chronic Phase Chronic Myeloid Leukemia (CML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4471-4471
Author(s):  
Jason N Berman ◽  
Wenda Greer ◽  
Ridas Juskevicius ◽  
Conrad V Fernandez ◽  
Mark Bernstein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Health Centre ◽  
Chronic Phase ◽  
Transcript Level ◽  
Transcript Levels ◽  
Significant Difference

Abstract Abstract 4471 Chronic myeloid leukemia (CML) is associated with the reciprocal t(9;22)(q34;q11) translocation, which generates the BCR-ABL fusion oncogene and is the most common myeloproliferative disease affecting adults. The clinical outcome in this disease has been revolutionized with the use of imatinib mesylate (Gleevec), a targeted tyrosine kinase inhibitor, and molecular surveillance, with the development of quantitative PCR (qPCR) approaches to measure BCR-ABL transcript levels. A number of guidelines outlining follow-up strategies for patients with chronic phase CML on imatinib therapy have been established. Once a patient is stable, a typical recommendation includes peripheral blood (PB) monitoring by qPCR of BCR-ABL levels every 3–6 months to determine response or relapse, with consideration of annual bone marrow (BM) examinations to assess for cytogenetic evolution. At the Queen Elizabeth II Health Sciences Centre and IWK Health Centre in Halifax, Nova Scotia, 34 patients with chronic phase CML on imatinib were identified from 2006 to 2008, with 36 paired samples, where transcript levels were assessed in both PB and BM within one week of each other. In 24 of the cases, the BCR-ABL transcript levels in PB and BM were within 0.5 log values of each other. In the remaining 12 cases, BCR-ABL transcript levels differed by greater than 0.5 log. Three cases had higher BM levels, but surprisingly, 9 patients had a higher BCR-ABL transcript level in the PB. In all cases, BCR-ABL levels were assessed by Q-RT-PCR using the ABI7500 instrument and primers and probe designed to detect p210 and p190 breakpoints. Results were recorded as a ratio of %BCR-ABL to GAPDH that was amplified as an internal control. There was no significant difference in clinical, morphological or laboratory parameters between these patients and others who had comparable PB and BM BCR-ABL levels. These findings highlight the need to compare BCR-ABL transcript levels derived from the same tissue during longitudinal monitoring. Moreover, while potentially due to stochastic factors, the striking observation of higher PB BCR-ABL transcript levels raises the question of which tissue represents the most accurate source for monitoring of BCR-ABL transcript levels and whether there is value in confirming a significant change in PB transcript level with BM evaluation. The discrepant levels in PB and BM could not be attributed to technical issues; the timing of sample processing from collection and quality of mRNA were comparable and no variability was observed in GAPDH levels to account for the difference. Without a technical explanation, the mechanism underlying this phenomenon remains uncertain. We speculate that it may reflect CML stem cell geography with one possibility being that the CML niche may be located external to the BM. Further studies are needed to confirm these observations. If corroborated, then revision of surveillance approaches for chronic phase patients may be indicated. Disclosures: No relevant conflicts of interest to declare.

Efficacy Of Different Therapeutic Approaches In Blastic Phase Of Chronic Myeloid Leukemia: Single Centre Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5173-5173
Author(s):  
Elza Lomaia ◽  
Ekaterina Romanova ◽  
Larisa Girshova ◽  
Yulia Alexeeva ◽  
Eugenia Sbityakova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Therapy ◽  
Advanced Phase ◽  
Blastic Phase

Abstract Dramatic changes in overall survival of patients (pts) with chronic myeloid leukemia (CML) in chronic phase (CP) have occurred since tyrosine kinase inhibitors (TKIs) were implemented in the treatment strategy. But there are still many issues in therapy of advanced phase disease, especially in blastic phase (BP). Allogeneic stem cell transplantation (alloSCT) is still the only curative option for CML BP, so all efforts should be focused on bringing pts to alloSCT. Thus optimal approach to obtain at least stable hematologic response before alloSCT is needed. Since 2008, 14 pts (4 more pts with isolated extramedullary BP were not included) with CML BP were admitted to our clinic. These were 8 males and 6 females with a median age of 44 years (range; 21-63) at the time of BP. The types of BP were: biphenotypic (n=1), undifferentiated (n=1), myeloid (n=8) and lymphoid (n=4). All pts except 2 (1 with BP and 1 with accelerated phase) were initially diagnosed as CP. Median time from diagnosis to BP was 37 months (range; 0-83). Before BP all pts except 2 were pretreated with imatinib and 6 of them, after failing imatinib, received one or more new TKIs. First line therapy in BP was monotherapy with new TKI (n=5) or chemotherapy (“7+3”, “RACOP”, low doses of Ara-C, “Hyper-CVAD”, “Dexa+VCR”) with or w/o TKI (n=9). Responses are specified in table 1. FLAG regimen was subsequently given to 5 pts as second or more line therapy after failure of previous monoTKI (n=1) or Rx + TKI (n=4). Median time from BP to FLAG was 3,5 months (range; 1,5-21). The best response to FLAG therapy was complete hematologic (n=1), complete cytogenetic with (n=1) or w/o (n=1) major molecular response. There were no responses in 2 cases. All responders maintain their response after median follow up (FU) of 2 months (range; 1,5-5). All patients treated with FLAG are alive (2 after alloSCT, 3 pending alloSCT). Only 1 ptn reached alloSCT w/o any Rx after monoTKI. AlloSCT was successful in 4/5. Median FU time for patients alive after alloSCT is 12 months (range; 3,5-25). For whole group after a median FU of 14 months, 7/14 (50%) pts are alive, including 4 pts after alloSCT. Estimated 3-year overall survival for all pts is 54% (fig. 1). Conclusion All CML BP patients treated with TKIs alone lost their response in a short time. Responses were much more durable in pts treated with Rx +/- TKIs. FLAG regimen was effective even in pts with failure to previous Rx+TKIs. The majority of pts after alloSCT are alive. Chemotherapy, including FLAG with concomitant or subsequent TKIs, had advantage over monoTKI both in overall and progression free survival in CML BP. Disclosures: Lomaia: Novartis: Honoraria, Travel grants Other; Bristol-Myers Squibb: Honoraria, Travel grants, Travel grants Other. Zaritskey:University of Heidelberg: Research Funding.

scholarly journals An Atypical Initial Presentation of Chronic Myeloid Leukemia with Central Nervous System and Lymph Node Blast Crises

2016 ◽  
Vol 9 (2) ◽  
pp. 415-421 ◽  
Author(s):  
Khadega A. Abuelgasim ◽  
Saeed Alshieban ◽  
Nada A. Almubayi ◽  
Ayman Alhejazi ◽  
Abdulrahman R. Jazieh
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Chronic Phase ◽  
Current Evidence ◽  
Molecular Response

We describe the case of a young man with therapy-naive chronic myeloid leukemia who did not initially have any peripheral blood or bone marrow excess blasts but presented with extramedullary myeloid blast crises involving the central nervous system and multiple lymph nodes. Conventional cytogenetic tests were positive for t(9;22)(q34:q11) as well as for trisomy 8, 14 and 21 and del(16q). The patient’s peripheral blood and bone marrow were positive for the BCR-ABL oncogene when analyzed by fluorescence in situ hybridization and polymerase chain reaction. He achieved good clinical, radiological, cytogenetic and molecular response to acute myeloid leukemia induction chemotherapy combined with 16 doses of triple intrathecal chemotherapy and oral dasatinib (second-generation tyrosine kinase inhibitor) treatment. Due to his poor general condition, he was treated with 24 Gy of whole-brain radiation therapy, as allogeneic stem cell transplantation was not feasible. Although extramedullary CNS blast crises are usually associated with a very poor outcome, our patient remains in complete cytogenetic and molecular remission, on single-agent dasatinib, 4 years after the diagnosis with no current evidence of active extramedullary disease. This suggests that dasatinib has a role in controlling not only chronic-phase chronic myeloid leukemia, but also its CNS blast crisis.

Targeting β-arrestin2 Enhances Survival in a Murine Model of Chronic Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 857-857
Author(s):  
Lindsay A.M. Rein ◽  
Minyong Chen ◽  
Barbara S. Theriot ◽  
James W. Wisler ◽  
Laura M. Wingler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Male Mice ◽  
Donor Cells ◽  
Wbc Count

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm of hematopoietic stem cells characterized by presence of a dysregulated BCR-ABL fusion protein which leads to constitutive activation of tyrosine kinase activity. Classically, CML is treated with tyrosine kinase inhibitors (TKIs). However, TKI therapy is non-curative, and persistence of quiescent leukemia stem cells likely accounts for the inability of these agents to cure CML. β-arrestins are multifunctional adapter proteins which regulate G protein-coupled receptor (GPCR) signaling and trafficking and have recently been identified as mediators of distinct cellular signaling cascades independent of G proteins. β-arrestins also play a role in the Smoothened/Hedgehog pathway, as well as in the Wingless/Frizzled (Wnt/Fz) signaling axis, both of which have been associated with the development of CML. We, therefore, hypothesize that β-arrestin2 (βarr2) is necessary for the development and propagation of CML and may function as a therapeutic target. Aim Demonstrate that loss of βarr2, using an inducible conditional knockout mouse model, slows progression of CML. Methods We used a standard murine retroviral transduction system to model chronic phase BCR-ABL positive CML. KLS cells (Lin-, Sca-1+, c-kit+) were harvested from bone marrow of donor C57BL6/J βarr2F/F-CreERT2+/- (Cre positive, CD45.2) and age matched C57BL6/J βarr2F/F-CreERT2-/- (Cre negative, CD54.2) male mice. KLS cells were retrovirally transduced with MSCV-BCR-ABL-IRES-GFP and were subsequently injected retro-orbitally into sublethally irradiated congenic wild type recipient male mice (CD45.1). Donor mice were engineered using global Cre-ER/loxP technology in order to induce site-specific recombination and loss of βarr2 when treated with tamoxifen. Mice who received Cre positive cells lost βarr2 only in hematopoietic cells. Recipient mice were treated with tamoxifen 75mg/kg daily via intraperitoneal injection for 5 days starting day 3 after transplant and were monitored for signs of leukemia development. Weekly blood analysis included WBC count, number of donor cells by flow cytometry, blood film, and qPCR for BCR-ABL expression. Survival was compared between animals receiving Cre positive (βarr2F/F-CreERT2+/-) and Cre negative (βarr2F/F-CreERT2-/-) donor cells as well as both tamoxifen treated and untreated conditions. Results Treatment of donor C57BL6/J βarr2F/F-CreERT2+/- mice with tamoxifen resulted in decreased βarr2 expression within 10 days in multiple tissues including spleen and bone marrow. By day 10, βarr2 expression was 9.5 ± 3.0% in Cre positive mice relative to pretreatment expression levels (Figure 1). In total, 8 mice received Cre positive cells and 11 mice received Cre negative cells. Ten of 11 (90.9%) Cre negative mice developed CML as evidenced by splenomegaly, leukocytosis, increased BCR-ABL expression measured by qPCR and increased number of donor cells detectable by flow cytometry. Median survival was 15 days. Six of 8 (75%) Cre positive mice developed disease with median survival of 27 days (HR 3.2, 95% CI; 1.525-12.2, p=0.013)(Figure 2). At day 11, flow cytometry for donor CD45.2 cells present in peripheral blood of recipient mice was 38 ± 2.05% in Cre negative versus 16.5± 3.9% in Cre positive mice (p<0.0001). Spleen size at death and WBC count at day 11 were not significantly different between groups. Conclusions These data demonstrate that targeting βarr2 prolongs the course of disease in chronic phase CML and raise the possibility that loss of βarr2 after disease onset may lead to disease regression. βarr2 may therefore represent an alternative therapeutic target for CML independent of tyrosine kinase inhibition. Disclosures: No relevant conflicts of interest to declare.

Chronic Myeloid Leukemia Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2911-2915 ◽  
Author(s):  
Edward Kavalerchik ◽  
Daniel Goff ◽  
Catriona H.M. Jamieson
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Chronic Phase ◽  
Leukemia Stem Cells ◽  
Molecular Events ◽  
Advanced Phase ◽  
Dividing Cells

Although rare, chronic myeloid leukemia (CML) represents an important paradigm for understanding the molecular events leading to malignant transformation of primitive hematopoietic progenitors. CML was the first cancer to be associated with a defined genetic abnormality, BCR-ABL, that is necessary and sufficient for initiating chronic phase disease as well as the first cancer to be treated with molecular targeted therapy. Malignant progenitors or leukemia stem cells (LSCs) evolve as a result of both epigenetic and genetic events that alter hematopoietic progenitor differentiation, proliferation, survival, and self-renewal. LSCs are rare and divide less frequently, and thus, represent a reservoir for relapse and resistance to a molecularly targeted single agent. On subverting developmental processes normally responsible for maintaining robust life-long hematopoiesis, the LSCs are able to evade the majority of current cancer treatments that target rapidly dividing cells. Enthusiasm for the enormous success of tyrosine kinase inhibitors at controlling the chronic phase disease is tempered somewhat by the persistence of the LSC pool in the majority of the patients. Combined therapies targeting aberrant properties of LSC may obviate therapeutic resistance and relapse in advanced phase and therapeutically recalcitrant CML.

BCR/ABL mRNA and the P210BCR/ABL Protein Are Downmodulated by Interferon- in Chronic Myeloid Leukemia Patients

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2200-2207 ◽  
Author(s):  
Fabrizio Pane ◽  
Ilaria Mostarda ◽  
Carmine Selleri ◽  
Rossella Salzano ◽  
Anna Maria Raiola ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Single Agent ◽  
Chronic Phase ◽  
Dependent Manner ◽  
Complete Hematologic Response ◽  
Ifn Treatment

The BCR/ABL hybrid gene plays a central role in the pathogenesis of the chronic phase of chronic myeloid leukemia (CML). We used a very sensitive quantitative reverse transcriptase-polymerase chain reaction to investigate the levels of hybrid BCR/ABL mRNA in bone marrow cells of 20 patients with Philadelphia positive (Ph+) CML treated with interferon- (IFN-) as a single agent. Bone marrow samples were collected at diagnosis and at hematologic remission induced by IFN-, or by hydroxyurea in case of resistance to IFN-. The mean levels of BCR/ABL transcripts in bone marrow mononuclear cells of patients who showed a complete hematologic response to IFN- were significantly reduced with respect to those at diagnosis (48 × 103v168 × 103; P &lt; .001), whereas no difference was detected between the values at diagnosis and at hematologic remission in patients resistant to IFN-. In cell culture experiments, IFN- priming significantly reduced the levels of BCR/ABL hybrid transcripts in a dose-dependent manner in Ph+ bone marrow precursors obtained at diagnosis from patients who subsequently responded to IFN- treatment (P &lt; .005). No downmodulation was observed in bone marrow precursors from patients who subsequently proved to be IFN-resistant. These results indicate that downmodulation of BCR/ABL gene expression could be one of the mechanisms involved in the response of CML patients to IFN- treatment.

scholarly journals Efficacy and Tolerability after Unusually Low Doses of Dasatinib in Chronic Myeloid Leukemia Patients Intolerant to Standard-Dose Dasatinib Therapy

2010 ◽  
Vol 4 ◽  
pp. CMO.S6413 ◽  
Author(s):  
Mariana Serpa ◽  
Sabri S. Sanabani ◽  
Israel Bendit ◽  
Fernanda Seguro ◽  
Flávia Xavier ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Chronic Phase ◽  
Patient Treatment ◽  
Hematological Toxicity ◽  
Drug Discontinuation ◽  
Once Daily ◽  
Starting Dose

We report our experience in 4 patients with chronic myeloid leukemia (CML) who had discontinued imatinib as a result of adverse events and had switched to dasatinib. The chronic phase ( n 2) and accelerated phase ( n 2) CML patients received dasatinib at starting dose of 100 and 140 mg once daily, respectively. Reappearance of hematological toxicity was observed in 3 patients and pancreatitis in one patient. Treatment was given at a lower dose and patients were followed. The median follow-up was 13 months and the median dose of dasatinib until achievement of complete cytogenetic remission (CCyR) was 60 mg daily (range = 20 to 120 mg). All four patients had achieved CCyR at a median of 4 months (range = 3 to 5 months) and among them, three had also achieved major molecular remission. We conclude that low-dose dasatinib therapy in intolerant patients appears safe and efficacious and may be tried before drug discontinuation.

scholarly journals Expression of Bcl-2 protein and the amplification of c-myc gene in patients with chronic myeloid leukemia

2006 ◽  
Vol 63 (4) ◽  
pp. 364-369 ◽  
Author(s):  
Milica Strnad ◽  
Goran Brajuskovic ◽  
Natasa Strelic ◽  
Biljana Zivanovic-Todoric ◽  
Ljiljana Tukic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Alkaline Phosphatase ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Chronic Phase ◽  
Blast Transformation ◽  
Hematopoietic Stem ◽  
Myc Gene

Background/Aim. Chronic myeloid leukemia (CML) represents a malignant myeloproliferative disease developed out of pluripotent hematopoietic stem cell that contains the fusion bcr-abl gene. Disorders that occur in the process of apoptosis represent one of the possible molecular mechanisms that bring about the disease progress. The aim of our study was to carry out the analysis of the presence of the amplification of the cmyc oncogene, as well as the analysis of the changes in the expression of Bcl-2 in the patients with CML. Methods. Our study included 25 patients with CML (18 in chronic phase, 7 in blast transformation). Using an immunohistochemical alkaline phosphatase-anti-alkaline phosphatase (APAAP) method, we analyzed the expression of cell death protein in the mononuclear bone marrow cells of 25 CML patients. By a differential PCR (polymerase chain reaction) method, we followed the presence of amplified c-myc gene in mononuclear peripheral blood cells. Results. The level of the expression of Bcl-2 protein was considerably higher in the bone marrow samples of the patients undergoing blast transformation of the disease. The amplification of c-myc gene was detected in 30% of the patients in blast transformation of the disease. Conclusion. The expression of Bcl-2 protein and the amplification of c-myc gene are in correlation with the disease progression.

scholarly journals Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 801-807 ◽  
Author(s):  
T Leemhuis ◽  
D Leibowitz ◽  
G Cox ◽  
R Silver ◽  
EF Srour ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Progenitor Cells ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Polymerase Chain Reaction Analysis ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem

Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ cells were isolated using centrifugal elutriation, monoclonal antibody labeling, and flow cytometric cell sorting. Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR/ABL translocation characteristic of CML. The CD34+DR+ subpopulation contained BCR/ABL(+) cells in 11 of 12 marrow samples studied, whereas the CD34+DR- subpopulation contained BCR/ABL(+) cells in 6 of 9 CML marrow specimens. These cell populations were assayed for hematopoietic progenitor cells, and individual hematopoietic colonies were analyzed by PCR for their BCR/ABL status. Results from six patients showed that nearly half of the myeloid colonies cloned from CD34+DR- cells were BCR/ABL(+), although the CD34+DR- subpopulation contained significantly fewer BCR/ABL(+) progenitor cells than either low-density bone marrow (LDBM) or the CD34+DR+ fraction. These CD34+ cells were also used to establish stromal cell-free long-term bone marrow cultures to assess the BCR/ABL status of hematopoietic stem cells within these CML marrow populations. After 28 days in culture, three of five cultures initiated with CD34+DR- cells produced BCR/ABL(-) cells. By contrast, only one of eight cultures initiated with CD34+DR+ cells were BCR/ABL(-) after 28 days. These results indicate that the CD34+DR- subpopulation of CML marrow still contains leukemic progenitor cells, although to a lesser extent than either LDBM or CD34+DR+ cells.

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

2018 ◽  
Vol 140 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Fiorina Giona ◽  
Michelina Santopietro ◽  
Giuseppe Menna ◽  
Maria Caterina Putti ◽  
Concetta Micalizzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Real Life ◽  
Chronic Phase ◽  
Optimal Management ◽  
Molecular Monitoring ◽  
Italian Experience ◽  
Adults And Children

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.

Sign in / Sign up

Export Citation Format

Share Document