Incidence and management of myelosuppression in patients with chronic- and accelerated-phase chronic myeloid leukemia treated with omacetaxine mepesuccinate.

Omacetaxine mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.

Rapid amelioration of hyperglycemia facilitated by dasatinib in a chronic myeloid leukemia patient with type 2 diabetes mellitus.

Tyrosine kinase inhibitors (TKIs) have been shown to affect glucose metabolism in patients with chronic myeloid leukemia (CML); however, their precise mechanism of action remains unknown. We herein report the case of a 57-year-old diabetic CML patient who was resistant to imatinib and initially required 20 units of insulin daily to control his blood glucose levels. After the initiation of dasatinib, the patient's insulin requirements declined rapidly and insulin treatment was discontinued within two weeks. Meanwhile, the fasting C-peptide immunoreactivity increased two-fold, suggesting that dasatinib facilitated the recovery of insulin production. Dasatinib may therefore be beneficial for diabetic CML patients, especially those who require insulin treatment.

[Acquired ichthyosis and haematological malignancies: five cases]. / Ichtyose acquise et hémopathie maligne : cinq observations.

BACKGROUND: Acquired ichthyosis is a rare condition that can reveal an unsuspected haematological malignancy, thus allowing early diagnosis and management. If ichthyosis regresses under treatment for the haematological disorder, its recurrence reflects a turning point in the course of the disease and implies worsening of the prognosis. PATIENTS AND METHODS: The patients were examined at a joint dermatology/haematology consultation. The diagnosis of ichthyosis was based on clinical examination alone with no patients undergoing skin biopsy. RESULTS: Our series included three men and two women aged 38 to 65 years consulting for a variety of reasons including asthenia, anaemia and adenopathy. Ichthyosis occurred 2 to 9 months after the initial symptoms of the blood disease. Lesions consisted of diffuse brown scales. The disease was associated with lymphadenopathy and biological inflammatory syndrome. Two patients were presenting non-Hodgkin lymphoma, one had Hodgkin's disease, one had chronic myeloid leukaemia in progression and one had an undifferentiated lymphomatous process. Treatment was based on chemotherapy and emollients. The ichthyosis progressed in step with the underlying malignancy in all cases, with regression being complete in three cases, partial in one case and absent in one case. DISCUSSION: In rare cases, acquired ichthyosis reveals systemic disease, and may be of infectious, endocrine or drug origin; it may also be idiopathic. However, it is most often a paraneoplastic syndrome with cutaneous expression encountered during haematological malignancies. Because of the variety of causative blood dyscrasias, ichthyosis cannot be used to guide their diagnosis, although it remains a reliable monitoring tool. CONCLUSION: Acquired ichthyosis should prompt the clinician to search for a neoplastic condition, primarily a haematological disorder, guided by other associated signs, given that in our study, skin lesions generally appear to precede signs of the blood disease.

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study.

Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.

A successful cord blood transplant in a child with second accelerated phase chronic myeloid leukemia following lymphoid blast crisis.

We describe a 5-year-old girl with Ph(+) CML who received a cord blood transplant in a second accelerated phase after a very early lymphoid blast crisis. She was induced into CR by ALL-directed chemotherapy and then maintained with IFN-alpha2b together with weekly rotational chemotherapy. Nineteen months after diagnosis, her mother gave birth to an HLA-compatible sibling, whose cord blood was cryopreserved. The patient's second acceleration occurred 22 months after the CML diagnosis. The subsequent conditioning regimen included busulfan 16 mg/kg, Ara-C 12 g/m2 and melphalan 140 mg/m2. In order to prevent GVHD, CsA alone was administered, 3 mg/kg i.v. per day for a total of 40 days. The total number of nucleated cells infused was 0.8 x 108/kg, with CD34+ cells 1.8 x 106/kg and CFU-GM 1 x 104/kg. Engraftment occurred on day +35. Respiratory distress, severe VOD and grade II acute gastrointestinal GVHD complicated the post-transplant period. No chronic GVHD occurred. The girl is alive 23 months after transplantation with complete donor chimerism; both Ph chromosome and bcr/abl RNA are negative. Bone Marrow Transplantation (2000) 25, 213-215.

Pulmonary fibrosis with megakaryocytoid cell infiltration in accelerated phase of chronic myelogenous leukaemia.

We report a patient in the accelerated phase of Philadelphia-chromosome-positive chronic myelogenous leukaemia who developed fibrosis in lungs, spleen and bone marrow. In the lungs, fibrosis was demonstrated in the alveolar septa which had been infiltrated by giant, bizarre-shaped cells resembling the megakaryocytes in the bone marrow. The relationship between the fibrosis and megakaryocytoid cell infiltration in the lungs is discussed.

Central catheter infection by Trichosporon beigelii after autologous blood stem cell transplantation. A case report and review of the literature.

A case of localized Trichosporon beigelii infection is reported in a 40-year-old woman with Ph+ chronic granulocyte leukemia who underwent autologous blood stem cell transplantation. On day +14 after autograft, while severely neutropenic, she developed a local infection involving the soft tissues surrounding the central venous catheter (CVC) point of entry into the subclavian vein. Trichosporon beigelii was isolated from culture of the CVC tip; resolution occurred after removal of the CVC, neutrophil recovery and antifungal treatment with amphotericin B and 5-fluorocytosine. To our knowledge this is the first case of CVC localized infection from Trichosporon beigelii after transplantation.

[Causes of death in chronic myeloid leukemia. Analysis of 109 patients]. / Causas de muerte en la leucemia mieloide crónica. Análisis de 109 pacientes.

The cause of death was revised in 109 cases of Ph'-positive chronic myelogenous leukaemia (CML) who died in a 15-year period. The median survival of the series, which included eight patients with initial criteria of blastic crisis, was 33.7 months (ranging between 2 and 192). Eight patients (7.3%) died during the chronic phase of the disease, 7 (6.4%) in the accelerated phase, and 94 (86.3%) in the blastic crisis. The cause of death in the chronic phase was frequently unrelated to CML (a second malignancy, cirrhosis of the liver, suicide, in four cases as opposed to infection, haemorrhage of hyperuricaemic renal failure in four others), but this was not so in the deaths occurred in the accelerated phase or blastic crisis. Thus, most of the deaths appearing in the accelerated phase were due to infection or haemorrhage, whereas in the blastic crisis they were mainly due to infection (54 of the 94 cases), followed by haemorrhage and leucostasis. All in all, these three complications were responsible for 94% of the deaths occurring in that evolutive phase of CML.

Extramedullary blast crisis and hemolytic anemia in a patient with t(3p+;4q-) and rapidly evolving myelogenous leukemia.

We have reported the case of a patient with a rapidly evolving myelogenous leukemia associated with hemolytic anemia, extramedullary evolution, and an isolated translocation of the long arm of chromosome 4 to the short arm of chromosome 3. The hemolytic process was primarily extravascular and was not associated with pyruvate kinase or glucose-6-phosphate dehydrogenase deficiency. Although blasts were absent from the peripheral smear and represented less than 10% of the bone marrow myeloid precursors, multiple organs including the heart, liver, lungs, and spleen were infiltrated with blasts at autopsy.