Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia without hitting leukemic stem cells

Background

Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia – regardless of the significant reduction of disease burden during treatment – since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited.

Design and Methods

We studied the natural history of a large cohort of virtual patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy using a computational model of hematopoiesis and chronic myeloid leukemia that takes into account stochastic dynamics within the hematopoietic stem and early progenitor cell pool.

Results

We found that in the overwhelming majority of patients the leukemic stem cell population undergoes extinction before disease diagnosis. Hence leukemic progenitors, susceptible to tyrosine kinase inhibitor attack, are the natural target for chronic myeloid leukemia treatment. Response dynamics predicted by the model closely match data from clinical trials. We further predicted that early diagnosis together with administration of tyrosine kinase inhibitor opens the path to eradication of chronic myeloid leukemia, leading to the wash out of the aberrant progenitor cells, ameliorating the patient’s condition while lowering the risk of blast transformation and drug resistance.

Conclusions

Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia, although it may have to be prolonged. The depth of response increases with time in the vast majority of patients. These results illustrate the importance of stochastic effects on the dynamics of acquired hematopoietic stem cell disorders and have direct relevance for other hematopoietic stem cell-derived diseases.     

Early prediction of success or failure of treatment with second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia

Background

Second-generation tyrosine kinase inhibitors induce cytogenetic responses in approximately 50% of patients with chronic myeloid leukemia in chronic phase in whom imatinib treatment has failed. However, it has not yet been established which of the patients in whom imatinib treatment fails are likely to benefit from therapy with second-generation tyrosine kinase inhibitors.

Design and Methods

We analyzed a cohort of 80 patients with chronic myeloid leukemia who were resistant to imatinib and who were treated with dasatinib or nilotinib while still in first chronic phase. We devised a scoring system to predict the probability of these patients achieving complete cytogenetic response when treated with second-generation tyrosine kinase inhibitors.

Results

The system was based on three factors: cytogenetic response to imatinib, Sokal score and recurrent neutropenia during imatinib treatment. We validated the score in an independent group of 28 Scottish patients. We also studied the relationship between cytogenetic responses at 3, 6 and 12 months and subsequent outcome. We classified the 80 patients into three categories, those with good risk (n=24), intermediate risk (n=27) and poor risk (n=29) with 2.5-year cumulative incidences of complete cytogenetic response of 100%, 52.2% and 13.8%, respectively (P<0.0001). Moreover, patients who had less than 95% Philadelphia chromosome-positive metaphases at 3 months, those with 35% or less Philadelphia chromosome-positive metaphases at 6 months and patients in complete cytogenetic response at 12 months all had significantly better outcomes than patients with lesser degrees of cytogenetic response.

Conclusions

Factors measurable before starting treatment can accurately predict response to second-generation tyrosine kinase inhibitors. Cytogenetic responses at 3, 6 and 12 months may influence the decision to continue treatment with second-generation tyrosine kinase inhibitors.     

Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia

Background

Allogeneic hematopoietic cell transplantation is the main curative therapy for patients with chronic myeloid leukemia who do not respond to tyrosine kinase inhibitors. It has been proposed that non-human leukocyte antigen gene polymorphisms influence outcome after hematopoietic cell transplantation and could be used alongside traditional patient-donor and transplant characteristics to create a recipient risk profile associated with allogeneic hematopoietic cell transplantation.

Design and Methods

A previous study from the European Group for Blood and Marrow Transplantation showed that the absence of recipient tumor necrosis factor receptor II, absence of donor interleukin 10 ATA/ACC and presence of donor interleukin 1 receptor antagonist allele 2 genotypes were associated with decreased survival and increased non-relapse mortality in adult patients with chronic myeloid leukemia undergoing myeloablative human leukocyte antigen-identical sibling transplantation. To explore these associations in unrelated donor transplantation, these polymorphisms were genotyped in 383 adult patients with chronic myeloid leukemia who underwent hematopoietic cell transplantation from unrelated donors matched for 10/10 human leukocyte antigens.

Results

The polymorphisms were not associated with overall survival, non-relapse mortality, relapse or acute graft-versus-host disease in the unrelated donor cohort. Comparison of the unrelated donor and human leukocyte antigen-identical sibling cohorts showed differences in survival and clinical characteristics.

Conclusions

We did not confirm that non-human leukocyte antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia, possibly because of the strong association between clinical variables and outcome which masked more subtle genetic effects.     

ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug

Background

Inhibition of BCR-ABL tyrosine kinase activity has evolved as a mainstay of therapy for patients with chronic myeloid leukemia. However, a fraction of leukemic cells persists under targeted therapy and can lead to disease progression on cessation of treatment.

Design and Methods

We analyzed bone marrow progenitor cells with the side population phenotype, and characterized the role of the intracellular ABC transporter A3 in imatinib detoxification.

Results

BCR-ABL-positive leukemic cells contribute to the side population cell compartment in untreated patients. Such leukemic side population cells, as well as CD34-positive progenitors from chronic myeloid leukemia samples, strongly express the intracellular ABCA3. Functionally, ABCA3 levels are critical for the susceptibility of chronic myeloid leukemia blast cell lines to specific BCR-ABL inhibition by imatinib. The transporter is localized in the limiting membrane of lysosomes and multivesicular bodies, and intracellular [¹⁴C]-labeled imatinib accumulates in such organelles. The lysosomal storage capacity increases with ABCA3 expression, thus regulating imatinib sequestration.

Conclusions

The intracellular ABC transporter A3 is expressed in chronic myeloid leukemia progenitor cells and may contribute to intrinsic imatinib resistance by facilitating lysosomal sequestration in chronic myeloid leukemia cells.     

Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed

Background

It has not been clearly established whether second-generation tyrosine kinase inhibitors actually improve the survival of patients with chronic myeloid leukemia in chronic phase who are given nilotinib or dasatinib therapy after treatment failure with imatinib.

Design and Methods

To address this issue we compared the survival of 104 patients in whom first-line therapy with imatinib failed and who were then treated with second-generation tyrosine kinase inhibitors with the outcome of 246 patients in whom interferon-α therapy failed and who did not receive tyrosine kinase inhibitor therapy.

Results

Patients treated with second-generation tyrosine kinase inhibitors had longer overall survival than the interferon controls (adjusted relative risk= 0.28, P=0.0001). However this survival advantage was limited to the 64.4% of patients in whom imatinib failed but who achieved complete cytogenetic response with the subsequent tyrosine kinase inhibitor (adjusted relative risk =0.05, P=0.003), whereas the 35.6% of patients who failed to achieve complete cytogenetic response on the second or third inhibitor had similar overall survival to that of the controls (adjusted relative risk=0.76, P=0.65).

Conclusions

Patients in whom imatinib treatment fails who receive sequential therapy with second-generation tyrosine kinase inhibitors have an enormous advantage in survival over controls (palliative therapy); this advantage is, however, limited to the majority of the patients who achieve a complete cytogenetic response.     

Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis

Background

Residual chronic myeloid leukemia disease following imatinib treatment has been attributed to the presence of quiescent leukemic stem cells intrinsically resistant to imatinib. Mesenchymal stromal cells in the bone marrow may favor the persistence and progression of leukemia by preserving the proliferation and self-renewal capacities of the malignant progenitor cells.

Design and Methods

BV173 or primary chronic myeloid leukemia cells were co-cultured with human mesenchymal stromal cells and imatinib-induced cell death was then measured. The roles of pro-and anti-apoptotic proteins and chemokine CXCL12 in this context were evaluated. We also studied the ability of BV173 cells to repopulate NOD/SCID mice following in vitro exposure to imatinib and mesenchymal stromal cells.

Results

Whilst imatinib induced dose-dependent apoptosis of BV173 cells and primary chronic myeloid leukemia cells, co-culture with mesenchymal stromal cells protected both types of chronic myeloid leukemia cells. Molecular analysis indicated that mesenchymal stromal cells reduced caspase-3 activation and modulated the expression of the anti-apoptotic protein Bcl-XL. Furthermore, chronic myeloid leukemia cells exposed to imatinib in the presence of mesenchymal stromal cells retained the ability to engraft into NOD/SCID mice. We observed that chronic myeloid leukemia cells and mesenchymal stromal cells express functional levels of CXCR4 and CXCL12, respectively. Finally, the CXCR4 antagonist, AMD3100 restored apoptosis by imatinib and the susceptibility of the SCID leukemia repopulating cells to the tyrosine kinase inhibitor.

Conclusions

Human mesenchymal stromal cells mediate protection of chronic myeloid leukemia cells from imatinib-induced apoptosis. Disruption of the CXCL12/CXCR4 axis restores, at least in part, the leukemic cells’ sensitivity to imatinib. The combination of anti-CXCR4 antagonists with tyrosine kinase inhibitors may represent a powerful approach to the treatment of chronic myeloid leukemia.     

Hypocellular acute myeloid leukemia in adults: analysis of the clinical outcome of 123 patients

Background

The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia.

Design and Methods

We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases.

Results

One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty-one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia.

Conclusions

The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia.     

The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up

Background

Imatinib mesylate is the first line treatment for chronic myeloid leukemia. The advent of imatinib increased survival significantly in patients in an advanced phase of the disease. However, few long-term data on the outcome of these patients based on large, prospective and controlled trials are available.

Design and Methods

A phase 2 multicenter trial of the use of imatinib 600 mg/daily in patients with accelerated phase chronic myeloid leukemia was sponsored and promoted by the Italian Cooperative Study Group on Chronic Myeloid Leukemia in 2001.

Results

One hundred and eleven patients were enrolled; the median follow-up of the 41 living patients is 82 months (range, 73–87). One hundred and seven patients (96%) returned to chronic phase and 79 patients (71%) achieved a complete hematologic response. Cumulative best rates of major cytogenetic response and complete cytogenetic response were 30% and 21%, respectively. All responses were maintained for a minimum of 4 weeks. At last follow-up, four patients were alive in complete remission after allogeneic transplant, 16 patients (14%) had switched to a second generation tyrosine kinase inhibitor and 21 patients (19%) were alive on imatinib therapy. No late toxicities were observed. Progression-free survival and event-free survival rates were 36.5% and 15%, respectively, at 7 years. The median survival time was 37 months, and was significantly associated with the achievement of a complete hematologic response or a complete cytogenetic response.

Conclusions

Imatinib may induce durable responses, associated with prolonged survival, in patients with accelerated phase chronic myeloid leukemia     

Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

Background

Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here.

Design and Methods

In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily.

Results

Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase.

Conclusions

Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition.     

Therapy-related myeloid neoplasms following treatment with radioiodine

Background

Few data are available on therapy-related myelodysplastic syndromes and acute myeloid leukemia developing after radioiodine treatment.

Design and Methods

We retrospectively analyzed 39 patients with myeloid neoplasms following radioiodine treatment, whose data were reported to the Duesseldorf Myelodysplastic Syndromes Register (8 of 3814 patients) and five other German Myelodysplastic Syndromes centers (n=31) between 1982 and 2011. These data were compared with those from 165 patients from our Myelodysplastic Syndromes Register with therapy-related myeloid neoplasms following chemotherapy (n=90), radiation (n=30), or radiochemotherapy (n=45).

Results

With a median latency of 79 months, 18 patients developed therapy-related acute myeloid leukemia and 21 presented with therapy-related myelodysplastic syndromes (8 refractory anemia with excess blasts I/II, 6 refractory anemia with multilineage dysplasia, 3 myelodysplastic syndromes with del(5q), 1 refractory anemia, 1 refractory anemia with ring sideroblasts, 1 chronic myelomonocytic leukemia II, 1 myelodysplastic/myeloproliferative neoplasm unclassifiable). Risk assessment according to the International Prognostic Scoring System was low-risk in 23%, intermediate-1 in 29%, intermediate-2 in 35%, and high-risk in 13%. Karyotype was abnormal in 68%, with chromosomes 7 (30%), 5 (26%), 8 (26%) and 3 (17%) being most frequently affected. No differences in the distribution of gender, World Health Organization subtype, acute myeloid leukemia progression, International Prognostic Scoring System score, and cytogenetic risk were observed between patients with therapy-related myeloid neoplasms following radioiodine or other treatment modalities. Of 17 patients who received induction chemotherapy, 71% were refractory to this treatment or died from treatment-related toxicity. The median overall survival in the entire group was 21.7 months (95%-CI 10.5–33 months) and did not differ significantly in comparison to the survival of patients with therapy-related myeloid neoplasms following other cytotoxic treatments. Patients with therapy-related acute myeloid leukemia had significantly inferior overall survival (12.4 versus 28.7 months, P=0.002).

Conclusions

Patients developing a therapy-related myeloid neoplasm after radioiodine treatment usually present with biological characteristics similar to those seen in patients with therapy-related myeloid neoplasms following other cytotoxic treatment modalities, associated with a low response rate to induction chemotherapy and poor prognosis.     

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Background

Comorbidities may affect survival and choice of treatment among cancer patients. In fact, comorbidities have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, breast cancer, head and neck cancer, and lung cancer. The Charlson comorbidity index and adult comorbidity evaluation-27 are lists of comorbidities with a weight assigned from 1 to 6 for the former and from 0 to 3 for the latter score, derived from relative risk estimates of a proportional hazard regression model using clinical data.

Design and Methods

We retrospectively evaluated the Charlson index and adult comorbidity evaluation-27 score in a cohort of 125 elderly (> 60 years) patients with chronic phase chronic myeloid leukemia who received dasatinib after showing resistance or intolerance to imatinib with the aim of establishing associations between comorbidities and the development of pleural effusions or compliance with the drug treatment.

Results

We found a significant association between the Charlson index as well as the adult comorbidity evaluation-27 score and the rate of drug reduction or suspension: with regards to the Charlson index, 49% of score 0 patients had a dose reduction compared to 63% of patients with score 1, 74% of those with score 2 and 100% of patients with score 3–5 (P=0.03); with regards to the adult comorbidity evaluation-27 score, 45% of patients had score 0–1 and 69% of patients with score 2–3 had a dose reduction. Of the 65 patients with Charlson score 0, 29% had at least one suspension of treatment (79% for hematologic and 21% for non-hematologic toxicity), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-hematologic toxicity) and 100% of patients with score 3 or 4 (all patients for both types of toxicity). High adult comorbidity index-27 scores identified patients at high risk of grade 3/4 hematologic toxicity. Forty-one patients (32.8%) experienced pleural effusion during treatment: the highest scores for both indices were associated with an increased risk of pleural effusions.

Conclusions

In elderly patients with chronic myeloid leukemia treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: stratification according to the Charlson index and adult comorbidity evaluation-27 score before dasatinib therapy may enable the identification of patients at risk of major toxicities.     

Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse

Background

Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse.

Design and Methods

Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy.

Results

Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission.

Conclusions

We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.     

Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population

Background

Biphenotypic acute leukemia is a rare disorder that is difficult to diagnose. It displays features of both myeloid and lymphoid lineage. There is still a lack of studies in biphenotypic acute leukemia in a Chinese population. We present here a comprehensive investigation of the clinical and biological characteristics, and outcome of biphenotypic acute leukemia in our hospital in over a seven year period.

Design and Methods

We retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and biphenotypic acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in biphenotypic acute leukemia patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period.

Results

Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as biphenotypic acute leukemia. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was T/B lymphoid and one (4.8%) was trilineage differentiation. When compared with acute myeloid leukemia and acute lymphoblastic leukemia, patients with biphenotypic acute leukemia showed significantly higher incidence of CD34 antigen expression, unfavorable karyotypes, and extramedullary infiltration (p<0.05). In this cohort of patients with biphenotypic acute leukemia, t(9;22) was the most common abnormality in chromosome structure. The median disease-free survival and overall survival in biphenotypic acute leukemia patients was five months and ten months, respectively, significantly shorter than those in acute myeloid leukemia and acute lymphoblastic leukemia patients (p<0.05).

Conclusions

The prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse.     

Phase I study of sorafenib in patients with refractory or relapsed acute leukemias

Background

Sorafenib is a multi-kinase inhibitor with activity against fms-like tyrosine kinase 3 with internal tandem duplication mutation and Raf kinase among others. A phase I dose escalation study of sorafenib was conducted in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias.

Design and Methods

Fifty patients received one of two different schedules; Schedule “A”: once or twice daily, five days per week, every week for a 21 day cycle, and Schedule “B”: once or twice daily, for 14 days every 21 days. Dose limiting toxicities were grade 3/4 hypertension, hyperbilirubinemia, and amylase elevation. The recommended phase II dose in hematologic malignancies is 400 mg twice daily for both schedules.

Results

Complete remissions or complete remissions with incomplete recovery of platelets were achieved in 5 (10%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Significant reduction in bone marrow and/or peripheral blood blasts was seen in an additional 17 (34%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Eleven of these responses (including 3 complete remissions/complete remissions with incomplete recovery) lasted for 2 cycles or beyond. In conclusion, sorafenib is active and well tolerated in acute myelogenous leukemia with fms-like tyrosine kinase 3 internal tandem duplication mutation.

Conclusions

Additional studies of sorafenib in patients with acute myelogenous leukemia, particularly those with fms-like tyrosine kinase 3 internal tandem duplication, are warranted, including sorafenib-based combinations. (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00217646","term_id":"NCT00217646"}}NCT00217646)     

Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies

Background

Although lenalidomide is very effective in the treatment of anemia of lower risk myelodysplastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients.

Design and Methods

Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodysplastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons.

Results

The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16).

Conclusions

Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort.