Chronic myeloid leukemia

April 20, 2009
Jorge E. Cortes, MD

Richard T. Silver, MD

Hagop M. Kantarjian, MD

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of the primitive hematopoietic stem cell. The disease is monoclonal in origin, affecting myeloid, monocytic, erythroid, megakaryocytic, B-cell, and, sometimes, T-cell lineages. Bone marrow stromal cells are not involved.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of the primitive hematopoietic stem cell. The disease is monoclonal in origin, affecting myeloid, monocytic, erythroid, megakaryocytic, B-cell, and, sometimes, T-cell lineages. Bone marrow stromal cells are not involved.

CML accounts for 15% of all leukemias in adults. Approximately 4,830 new cases of CML will be diagnosed in 2008, and it is estimated that 450 patients will die of CML this year. The incidence is 1.7 per 100,000 population. With imatinib (Gleevec) therapy, the annual mortality may be reduced significantly (less than 2%–3% per year).


Gender The male-to-female ratio is 1.1–1.4:1.

Age According to SEER (Surveillance, Epidemiology, and End Results) and MRC (Medical Research Council, UK) data, the median age of patients with CML is 66 years. However, most patients who are admitted to medical therapy studies are 50–60 years old, with a median age of ~53 years. Patients in bone marrow transplantation (BMT) studies are even younger, with a median age of ~40 years. Age differences must be considered in all studies because this variable may affect results.

Etiology and risk factors

The etiology of CML is unclear. Some associations with genetic and environmental factors have been reported, but in most cases, no such factors can be identified.

Genetic factors There is little evidence linking genetic factors to CML. Offspring of parents with CML do not have a higher incidence of CML than the general population.

Environmental factors Nuclear and radiation exposures, including therapeutic radiation, have been associated with the development of CML. Exposure to chemicals has not been consistently associated with greater risk.

Signs and symptoms

CML usually runs a biphasic or triphasic course. This process includes an initial chronic phase and a terminal blastic phase, which is preceded by an accelerated phase in 60%–80% of patients.

Chronic phase If untreated, chronic-phase CML is associated with a median survival of 3.5–5.0 years. During the chronic phase, CML is asymptomatic in 25%–60% of all cases and, in these cases, is discovered on a routine blood examination.

In symptomatic patients, the most common presenting signs and symptoms are fatigue, left upper quadrant pain or mass, weight loss, and palpable splenomegaly. Occasionally, patients with very high WBC counts may have manifestations of hyperviscosity, including priapism, tinnitus, stupor, visual changes from retinal hemorrhages, and cerebrovascular accidents.

Patients in chronic-phase CML do not have an increased risk for infection. Splenomegaly is documented in 30%–70% of patients. The liver is enlarged in 10%–20% of cases.

Accelerated phase This is an ill-defined transitional phase. The criteria (M. D. Anderson Cancer Center [MDACC]) used recently in all the studies with tyrosine kinase inhibitors include the presence of 15%–29% blasts, ≥ 30% blasts and promyelocytes, or ≥ 20% basophils in the peripheral blood or a platelet count < 100 × 109/L unrelated to therapy. Cytogenetic clonal evolution is also a criterion for acceleration. Other classifications include more subjective criteria (Table 1). The classification used may affect the expected outcome for a group of patients defined as accelerated phase. With imatinib therapy, the estimated 4-year survival rate exceeds 50%. Thus, a new definition of accelerated phase (ie, predictive for short survival) needs to be developed.

The accelerated phase is frequently symptomatic, including the development of fever, night sweats, weight loss, and progressive splenomegaly.

Blastic phase The blastic phase morphologically resembles acute leukemia. Its diagnosis requires the presence of at least 30% of blasts in the bone marrow or peripheral blood. The World Health Organization has proposed to consider blast phase with ≥ 20% blasts, but this classification has not been validated, and recent evidence suggests that patients with 20% to 29% blasts have a significantly better prognosis than those with ≥ 30% blasts. In some patients, the blastic phase is characterized by extramedullary deposits of leukemic cells, most frequently in the CNS, lymph nodes, skin, or bones.

Patients in blastic phase usually die within 3–6 months. Approximately 70% of patients in blastic phase have a myeloid phenotype; 25%, lymphoid; and 5%, undifferentiated. Prognosis is slightly better for a lymphoid blastic phase than for myeloid or undifferentiated cases (median survival 9 vs 3 months).

Patients in blastic phase are more likely to experience symptoms, including weight loss, fever, night sweats, and bone pain. Symptoms of anemia, infectious complications, and bleeding are common. Subcutaneous nodules or hemorrhagic tender skin lesions, lymphadenopathy, and signs of CNS leukemia may also occur.

Laboratory features

Peripheral blood The most common feature of CML is an elevated WBC count, usually > 25 × 109/L occasionally with cyclic variations. The finding of unexplained, persistent leukocytosis (eg, > 12–15 × 109/L) in the absence of infections or other causes of WBC count elevation should prompt a work-up for CML.

The WBC differential usually shows granulocytes in all stages of maturation, from blasts to mature, morphologically normal granulocytes. Basophils are elevated, but only 10%–15% of patients have ≥ 7% basophils in the peripheral blood. Frequently, eosinophils are also mildly increased. The absolute lymphocyte count is elevated at the expense of T lymphocytes.

The platelet count is elevated in 30%–50% of patients and is higher than 1,000 × 109/L in a small percentage of patients with CML. When thrombocytopenia occurs, it usually signals disease acceleration.

Some patients have mild anemia at diagnosis.

Neutrophil function is usually normal or only mildly impaired, but natural killer (NK) cell activity is impaired. Platelet function is frequently abnormal but usually has no clinical significance.

Bone marrow The bone marrow is hypercellular, with cellularity of 75%–90%. The myeloid-to-erythroid ratio is usually 10–30:1. All stages of maturation of the WBC series are usually seen, but the myelocyte predominates.

Megakaryocytes are increased in number early in the disease and may show dysplastic features. They are usually smaller than the typical normal megakaryocytes. Fibrosis may be evident at diagnosis but increases with disease progression and is usually an adverse prognostic finding.

Other laboratory findings Leukocyte alkaline phosphatase activity is reduced at diagnosis. Serum levels of vitamin B12 and transcobalamin are increased, sometimes up to 10 times normal values. Serum levels of uric acid and lactic dehydrogenase (LDH) are also frequently elevated.

Cytogenetic and molecular findings

Philadelphia chromosome CML is characterized by the Philadelphia (Ph) chromosome, which represents a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11.2). The c-abl proto-oncogene located in chromosome 9q34 encodes for a nonreceptor protein-tyrosine kinase expressed in most mammalian cells. In chromosome 22, the breakpoint occurs within the BCR gene and usually involves an area known as the major breakpoint cluster region (m-bcr), located either between exons b3 and b4 or between exons b2 and b3. Therefore, two different fusion genes can be formed, both of them joining exon 2 of abl with either exon 2 (b2a2) or exon 3 of bcr (b3a2). Among the 5% to 10% of patients who do not have the Ph chromosome detected by karyotyping, 30% to 40% have the molecular rearrangement identified by fluorescent in situ hybridization (FISH)/polymerase chain reaction (PCR). Those patients without this rearrangement are considered to have “atypical CML,” a unique entity with different prognosis and treatment.

Upon translation, a new protein with a molecular weight of 210 kd (p210BCR-ABL) is synthesized, which, compared with the normal c-abl, has markedly increased kinase activity and can transform transfected cells and induce leukemia in transgenic mice. Occasionally, the breakpoint can occur in other areas (m-bcr and µ-bcr), leading to different transcripts (eg, p190BCR-ABL and p230BCR-ABL, respectively). The mechanism of oncogenesis of p210BCR-ABL is unclear, but, upon phosphorylation, it can activate several intracellular pathways, including ras and the MAP kinase pathway, the Jak-Stat pathway, the PI3 kinase pathway, and the myc pathway. Ultimately, this leads to altered adhesion to extracellular matrix and stroma, constitutive activation of mitogenic signals, and inhibition of apoptosis.

Staging and prognosis

Staging systems Several characteristics of CML affect the prognosis, including age; spleen size; WBC and platelet counts; and percentage of blasts, eosinophils, and basophils in the peripheral blood. Deletions of the derivative chromosome 9 are identified in 10% to 15% of patients and have been associated with an adverse prognosis with most treatment modalities. Imatinib may overcome the adverse prognosis associated with del der(9). These factors have been incorporated into several staging systems.

Sokal’s classification A frequently used risk classification is Sokal’s prognostic risk system. In this system, the hazard ratio function is derived from the following formula: λi(+)/λo(t) = Exp 0.0116 (age – 43.4) + 0.0345 (spleen – 7.51) + 0.188 [(platelets/700)2 – 0.563] + 0.0887 (blasts – 2.10).

This risk classification defines three prognostic groups with hazard ratios of < 0.8, 0.8.–1.2, and > 1.2 (ie, low-, intermediate-, and high-risk).

The Hasford classification has been suggested to separate more clearly and without overlap risk groups among patients treated with interferon therapy. The Hasford score is derived from the formula (0.6666 × age [0 when age < 50 years; 1, otherwise] + 0.0420 × spleen size [cm below costal margin] + 0.0584 × blasts [%] + 0.0413 × eosinophils [%] + 0.2039 × basophils [0 when basophils < 3%; 1, otherwise] + 1.0956 × platelet count [0 when platelet count < 1,500 × 109; 1, otherwise]) × 1000. Based on the score, patients can be classified into three risk groups: low (score ≤ 780), intermediate (score > 780 and ≤ 1480), and high (≥ 1480). This classification may be less predictive in the imatinib era.



Conventional chemotherapy

Busulfan (Busulfex, Myleran) and hydroxyurea were the chemotherapeutic agents used most frequently in CML until the development of imatinib. Busulfan is now rarely used.

Hydroxyurea is most frequently used to control the WBC while confirming the diagnosis of CML. The usual dose of hydroxyurea is 40 mg/kg/d. The dose is then adjusted individually to keep the WBC count in a range between 4 and 10 × 109/L.

Neither busulfan nor hydroxyurea significantly reduces the percentage of cells bearing the Ph chromosome, and, therefore, the risk of transformation to the blastic phase is unchanged. Their use should be limited to temporary control of hematologic manifestations before definitive therapy (eg, imatinib, stem-cell transplantation) is instituted. Once the diagnosis of CML is confirmed, imatinib should be initiated immediately. There is no need or benefit to initially “debulking” with hydroxyurea.


Recombinant interferon (rIFN-α) can induce a complete hematologic response (Table 2) in 70%–80% of patients with CML, with some degree of suppression of Ph chromosome-positive cells (ie, cytogenetic response) in 40%–60% of patients, which is complete in up to 20%–25% of patients. Randomized studies have documented a survival advantage for patients treated with rIFN-α who achieved a major, and particularly a complete, cytogenetic response.

Patients who achieve a complete cytogenetic response have a 10-year survival rate of 75% or more.

Interferon and cytarabine (Ara-C) The combination of IFN-α and low-dose Ara-C induced a higher (ie, 40%–50%) response rate compared with rIFN-α alone, and possibly a survival advantage.

Approximately 30% of those achieving complete cytogenetic remission with IFN-α may achieve a sustained molecular remission and are probably cured. Among the others, 40% to 60% remain free of disease after more than 10 years despite the presence of minimal residual disease. This has been called “operational cure.”

Formulations of rIFN-α attached to polyethylene glycol (PEG-IFN) have a longer half-life that allows for weekly administration and may have decreased toxicity.

Imatinib is a potent inhibitor of the tyrosine kinase activity of BCR-ABL and a few other tyrosine kinases, such as PDGF-R (platelet-derived growth factor-receptor) and c-kit. It has demonstrated significant activity in patients with CML in all phases of the disease, whether they have received prior therapy or not. Among patients with chronic-phase CML for whom prior IFN-α therapy failed, 55%–85% of patients achieved a major cytogenetic remission, including 45%–80% with a complete cytogenetic remission. The estimated rate of survival free of transformation to accelerated with blast phase is 69% at 60 months. Among patients treated in early chronic-phase CML who had not received prior therapy, the rate of complete cytogenetic response is 82%, with an overall survival rate at 72 months of 93%, and event-free survival, 83%.

Overall and event-free survival with imatinib therapy is significantly better than what has been seen with other therapies. Thus, imatinib has become the standard therapy for CML (Figure 1). The proper management of patients receiving imatinib is important.

Dose The standard dose of imatinib is 400 mg daily for chronic phase and 600 mg for accelerated and blastic phases. Dose reductions may be needed in some patients because of toxicity, but doses less than 300 mg daily are not recommended. Available data from the phase I study show a clear decrease in the probability of response with doses lower than 300 mg daily. Several studies have suggested that starting therapy for patients in chronic phase with a higher dose of imatinib (600 or 800 mg daily) may improve the rate of complete cytogenetic and molecular responses and the event-free and progression-free survival with adequate tolerance. A randomized trial is currently ongoing to address whether the standard dose should be changed.

Toxicity Imatinib is well tolerated. However, a significant fraction of patients develop grade 1–2 adverse events, including nausea, peripheral or periorbital edema, muscle cramps, diarrhea, skin rashes, weight gain, and fatigue. These events frequently are minor and either do not require therapy or respond to adequate early intervention. Fluid retention responds to diuretics when indicated; diarrhea can be managed with loperamide or other agents; nausea usually responds to prochlor-perazine, promethazine, or other agents; muscle cramps can be managed with tonic water or quinine; skin rash may be managed with antihistamines and/or corticosteroids (topical and/or systemic).

Myelosuppression is the most common grade 3–4 adverse event. Neutropenia can be seen in up to 45% of patients, thrombocytopenia in up to 25% of patients, and anemia in 10% of patients. Treatment is held for grade ≥ 3 neutro­penia (neutrophil count < 109/L) or thrombocytopenia (platelet count < 50 × 109/L) and restarted when counts recover above these levels. If the recovery takes longer than 2 weeks, the dose may be reduced. Treatment interruptions and dose reductions are not usually recommended for anemia. Myelosuppression is much more likely to occur during the first 2 to 3 months of therapy and is best managed with treatment interruption and close monitoring. Hematopoietic growth factors (granulocyte colony-stimulating factor [G-CSF, filgrastim, Neupogen] and erythropoietin) have been used successfully to manage prolonged or recurrent myelosuppression but the long-term safety of this approach needs to be assessed.

Monitoring The treatment objective has evolved from hematologic responses (hydroxyurea) to cytogenetic responses (IFN-α), to molecular responses in the imatinib era. All patients have to be evaluated with cytogenetic analysis before the start of therapy, and a baseline quantitative PCR analysis is useful. Conventional cytogenetic analysis is important at baseline and for follow-up because it provides valuable information about the entire karyotype (ie, clonal evolution, cytogenetic abnormalities in Ph chromosome-negative cells) that cannot be obtained with FISH or PCR and has prognostic implications. A cytogenetic analysis every 3 to 6 months during the first year and every 6 to 12 months thereafter is recommended. Quantitative PCR is recommended every 3 to 6 months. It is inappropriate not to follow patients with cytogenetics and real-time PCR.

Duration of therapy At this time, the duration of therapy is unclear. A minority of patients have reached undetectable levels of disease by PCR, and few have discontinued therapy. This has usually resulted in relapse. Thus, until further evidence becomes available, patients should continue therapy indefinitely.

Allogeneic BMT

Allogeneic BMT is potentially curative in CML, although relapses and mortality from complications such as chronic graft-vs-host disease (GVHD) may occur many years after transplantation. Results are better for patients in the chronic phase than in either the accelerated or blastic phase. Long-term survival rates of 50%–80% and disease-free survival rates of 30%–70% can be achieved in the chronic phase. The role of BMT is now changing in view of the results obtained with imatinib.

Predictors of response Early BMT within the first 1–3 years after diagnosis may be associated with a better outcome than BMT later in the course of disease. Younger patients also have a better outcome than older patients, with those younger than age 20 to 30 having the best prognosis. The use of the European Bone Marrow Transplant (EBMT) score helps to separate those patients who may have a better outcome from those who will not.

Conditioning regimens, including total-body irradiation (TBI), have been traditionally used, but non–TBI-containing regimens (eg, with busulfan and cyclophosphamide [Cytoxan, Neosar]) have produced similar results. More recently, conditioning regimens using pharmacologic targeting of busulfan have been associated with decreased regimen-related toxicity while preserving the antileukemia effect.

Also, nonmyeloablative conditioning regimens frequently containing purine analogs (mini-BMT) have been tested recently to expand the use of transplants to older patients or to patients with medical conditions that preclude conventional BMT.

Graft-vs-host disease The major morbidity from BMT is GVHD. T-cell depletion of the graft can reduce the incidence of this complication but at the expense of higher relapse and graft failure rates. (For a full discussion of GVHD, see chapter 36.)

Alternatives to matched-related donors For patients who do not have a matched-related donor, matched unrelated donor (MUD) transplants are reasonable alternatives. The 9-year experience from the National Marrow Donor Program in 1,432 patients reported a 3-year survival rate of 37.5%. Early transplantation results in better outcome, with patients transplanted in chronic phase having a 3-year disease-free survival of 63%. The outcome of patients transplanted in accelerated, blastic, or second chronic phase is inferior.

Relapse after BMT Donor leukocyte infusions are the most effective strategy to treat patients who relapse after BMT. With this strategy, 70%–80% of patients can achieve a cytogenetic complete response; the best results are achieved when patients are treated during cytogenetic or molecular relapse. Imatinib has also been effective for patients who relapse after BMT. A complete hematologic response in > 70% of patients and a cytogenetic response in 58% have been reported, with the best responses obtained in patients relapsing in chronic phase.

Imatinib failure The most frequently identified mechanism of resistance to imatinib is the development of mutations at the Abl kinase domain. Mutations are identified in 40% to 60% of patients, with the most frequent occurring in the P-loop. Not all mutations confer the same level of resistance to imatinib, and some may be overcome by increased concentrations of imatinib. The most resistant mutation is T315I. Although P-loop mutations have been reported to be linked to a poor prognosis, this theory has not been confirmed in all studies and it is probably more appropriate to consider individual mutations rather than group them by location.

Changing therapy based on molecular responses cannot be justified in most instances at the present time. Even when patients who have not achieved a 3-log reduction in transcript levels after 12 months of therapy have an inferior prognosis compared with those with at least a 3-log reduction, they still have a 92% probability of disease progression-free survival at 3 years, and in most instances, this only represents a loss of cytogenetic response. If the proposed alternative treatment option has any significant risk of mortality, the risk may be unnecessary. The clinical significance of the presence of mutations in patients with an adequate response is still unclear. Thus, mutations should be investigated in patients with clinical evidence of failure. In this setting, a change of therapy is indicated whether a mutation is indicated or not, but in some instances specific mutations may guide the selection of therapy.

The European LeukemiaNet has established criteria for failure that have become standard (Table 3). These emphasize the response achieved and the time to such response. Patients who meet criteria for failure should be offered therapy with a second-generation tyrosine kinase inhibitor. For patients with suboptimal response there are no available data as to what the optimal management may be, although imatinib dose escalation is usually recommended. A second generation of tyrosine kinase inhibitors has been developed to overcome resistance to imatinib.

Two of these agents have recently gained regulatory approval (dasatinib [Sprycel] and nilotinib [Tasigna], and others are being developed (Bosutinib, INNO-406). Nilotinib was designed based on the imatinib structure, with modifications to improve its binding to BCR-ABL and increase its selectivity; these modifications result in an agent at least one order of magnitude more potent than imatinib against BCR-ABL. Dasatinib is structurally unrelated to imatinib and, in contrast to it, can bind both the inactive and active configurations of BCR-ABL. In addition, dasatinib is a dual inhibitor that blocks Src as well as Abl and is two orders of magnitude more potent than imatinib. Both agents have been shown to inhibit both the wildtype BCR-ABL and nearly all of the clinically significant mutants of BCR-ABL, except for T315I. The results from the initial clinical trials have been impressive.

Dasatinib The initial phase II trials used a dose of 70 mg twice daily. Significant clinical activity was seen in patients in all stages of the disease after imatinib resistance or intolerance, with complete cytogenetic responses in 53% in chronic phase, 33% in accelerated phase, 27% in myeloid blast phase, and 46% in lymphoid blast phase. Duration of response correlates with the stage of the disease, with progression free-survival of 80% at 24 months for those in chronic phase, and 46% in accelerated phase. In contrast, the median progression-free survival was 5.6 and 3.1 months, respectively, for those in myeloid and lymphoid blast phase. Some of the most significant adverse events include myelosuppression (grade 3-4 neutropenia and thrombocytopenia in nearly 50% each), pleural effusion, and gastrointestinal hemorrhage (particularly in the advanced stages). Alternative schedules may improve the toxicity profile. In a randomized study, dasatinib administered as 100 mg once daily was associated with significantly less myelosupression and pleural effusion compared to 70 mg twice daily (and to 50 mg twice daily or 140 mg once daily). The response to therapy was identical, with a trend toward improved progression-free survival with the 100 mg once daily schedule. Dasatinib is approved for treatment of patents with CML in all phases of the disease who have experienced resistance or intolerance to imatinib. The standard dose for patients in chronic phase is 100 mg once daily, and 70 mg twice daily for patients in advanced stages.

Nilotinib Significant activity has been documented in patients treated after imatinib failure with nilotinib 400 mg twice daily in phase II studies. Rates of CCgR for patients treated in chronic phase after imatinib resistance or intolerance were 42% and for those treated in accelerated phase 19%. Responses have been durable with a sustained MCyR at 18 months in 84% of patients treated in chronic phase. In accelerated phase progression-free survival is 57% at 12 months. The most significant toxicities reported have been myelosuppression (grade 3-4 neutropenia or thrombocytopenia in approximately 30%, each), and biochemical abnormalities (elevation of indirect bilirubin, lipase, and glucose) that have been usually transient and asymptomatic. There is also the potential for QTc prolongation (a class effect for all tyrosine kinase inhibitors), although less than 3% of patients have had significant prolongation, most frequently asymptomatic. Nilotinib is currently approved for treatment of patients in chronic or accelerated phase of the disease who have experienced resistance or intolerance to imatinib, and the standard dose is 400 mg twice daily. Nilotinib should be taken on an empty stomach as food may significantly increase the absorption.

Other agents Other investigational agents are being developed for patients who fail imatinib therapy. Bosutinib is another Src and Abl inhibitor with activity against most mutants of BCR-ABL. Early results auggest significant activity among patients who fail imatinib therapy. Bosutinib has minimal or no activity against PDGF-R and c-kit, which could lead to decreased toxicity (eg, pleural effusions and myelosuppression). INNO-406 has activity against Lyn and Abl and has also shown activity in patients who have failed imatinib and other tyrosine kinase inhibitors. Several agents are being developed to treat patients with the T315I mutation that is resistant to all available agents. These include homoharringtonine, MK-0457, XL-228, PHA-739358, DCC-2036, and AP24534. Early results from these trials suggest activity in some patients.

Treatment recommendations

The long-term results of imatinib are excellent with an overall survival of greater than 90% at 6 years. Thus, all patients in chronic phase should be offered standard-dose imatinib as initial therapy. Patients should be followed closely to determine that the expected results are met at the specified times (Table 3). If this is the case, treatment should continue uninterrupted indefinitely. For patients with suboptimal response, a dose escalation is recommended. For patients with failure to respond to imatinib, a change in therapy should be considered to one of the second-generation tyrosine kinase inhibitors.

Allogeneic stem cell transplant The role of transplant in CML has changed and nowadays it is considered mostly a second-line treatment option. For patients who fail imatinib therapy, transplant should be considered, although an initial trial with a second-generation tyrosine kinase inhibitor should be considered. Adequate response at early time points is important, particularly for young patients with a transplant option. If there is no cytogenetic response at 6 months or no major cytogenetic response by 12 months, transplant should be considered in such patients.



Imatinib is also effective for patients with CML in transformation. Seventy-one percent of patients in accelerated phase treated with 600 mg/d of imatinib had a hematologic response. The major cytogenetic response rate was 24%, with a time to disease progression of 12 months at 67%. These results are significantly superior to those with 400 mg/d, making 600 mg/d the standard dose in accelerated phase. In blast phase, 52% of patients achieved a hematologic remission and 31% a sustained remission lasting at least 4 weeks with imatinib. However, the median response duration is only 10 months, even when considering only patients with sustained remission (ie, lasting at least 4 weeks). Patients with clonal evolution have a lower probability of response and shorter survival than patients without clonal evolution when treated with imatinib.

Nilotinib and dasatinib also have significant clinical activity in patients with advanced stage disease. They should be considered for patients who have failed prior therapy, including imatinib.


Compared with those results in patients in chronic phase, results with allogeneic BMT are worse in patients in accelerated or blastic phase, with 4-year survival rates of only 10%–30%. Patients in accelerated phase (determined on the basis of clonal evolution only) who undergo BMT < 1 year after diagnosis have a 4-year probability of survival of 74%. Patients in blast phase who respond to therapy with a second-generation tyrosine kinase inhibitor should be offered a BMT in second chronic phase if an adequate donor is available.


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