Interruption or Discontinuation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukaemia: A Retrospective Cohort Study (SPARKLE) in Belgium.

OBJECTIVES: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with chronic myeloid leukaemia (CML). METHODS: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context) between May 2013 and May 2016. Data collection took place between October 2016 and February 2017. RESULTS: All 60 participants (69 interruptions/discontinuations) had chronic-phase CML and 75% had at least a major molecular response (≥MMR) at interruption/discontinuation. Most interruptions/discontinuations occurred while on imatinib (36/69; 49%) and dasatinib (20/69; 29%). Most interruptions/discontinuations occurred due to side effects/intolerance (46/69; 67%); other reasons included a wish to conceive (6/69; 9%) and attempts to achieve treatment-free remission (TFR) (6/69; 9%). Interruptions due to side effects occurred later for imatinib- or dasatinib-treated patients than for those on nilotinib or ponatinib. Treatment was re-initiated in 62% (43/69) of cases. Most interruptions caused by side effects/intolerance were followed by treatment changes. All 4 patients with ≥MR 4.5 at interruption/discontinuation and ≥11-month follow-up who had not restarted treatment maintained the response. CONCLUSION: Although TKIs are used for long-term CML treatment, physicians sometimes recommend interruptions/discontinuations. In this study, interruptions/discontinuations were mainly caused by side effects or intolerance, rather than TFR attempts.

Variant-specific BCR::ABL1 quantification discrepancy in chronic myeloid leukemia.

INTRODUCTION: Accurate quantification of the BCR::ABL1 fusion gene in whole blood is pivotal for the clinical management of chronic myeloid leukemia (CML) patients. The fusion protein encoded by BCR::ABL1 can vary in size, depending on the BCR and/or ABL1 gene breakpoint. The vast majority of CML patients have a p210 BCR::ABL1 fusion gene (M-BCR), which can be attributed to the presence of either e14a2 (b3a2) or e13a2 (b2a2) mRNA transcript junctions. METHODS: Twenty-five CML samples were analyzed in two different ISO15189-accredited centers that both use an Europe Against Cancer-based quantitative polymerase chain reaction (qPCR) protocol. Reanalysis of the sample set with transcript-specific standard curves and digital droplet PCR (ddPCR) were performed. RESULTS: qPCR quantification revealed a significant (up to 1 log) difference specifically for the e13a2 transcript variant in contrast to e14a2 transcripts (Hodges-Lehman 4.29; p < 0.001). Reanalysis of the sample set with transcript-specific standard curves abolishes the initial transcript-specific difference (Hodges-Lehman 0.003; p = 0.8192). Comparison of transcript-specific qPCR results of both centers with ddPCR, an absolute quantification method, showed a statically significant association, especially in the lower range, indicating the clinical utility of transcript-specific or absolute quantification methods. CONCLUSION: Our data show that differences between transcript-specific quantification might exist between centers, leading to potential clinical impact on the follow-up of CML patients. The use of transcript-specific standard curves for qPCR quantification, or absolute quantification, can significantly reduce these differences. Specific attention should be applied to the interpretation of quantification differences of CML patients that switch between diagnostic centers.

Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with hematological malignancies.

OBJECTIVE: To compare the characteristics and outcome of patients with hematological malignancies referred to the ICU with severe sepsis and septic shock who had or had not received recent intravenous chemotherapy, defined as within 3 weeks prior to ICU admission. DESIGN AND SETTING: Retrospective observational cohort study on prospectively collected data in a medical ICU of a university hospital. PATIENTS: 186 ICU patients with hematological malignancies with severe sepsis or septic shock (2000-2006). MEASUREMENTS AND RESULTS: There were 77 patients admitted with severe sepsis and 109 with septic shock; 91 (49%) had received recent intravenous chemotherapy. Patients with recent chemotherapy more often had a high-grade malignancy and were more often neutropenic, less often had pulmonary infiltrates, and less often required mechanical ventilation. ICU, 28-day, in-hospital, and 6-month mortality rates were 33% vs. 48.4%, 40.7% vs. 57.4%, 45.1% vs. 58.9%, and 50.5% vs. 63.2% in patients with and without recent chemotherapy, respectively. Logistic regression identified four variables independently associated with 28-day mortality: SOFA score at ICU admission, pulmonary site of infection, and fungal infection were associated with worse outcome whereas previous intravenous chemotherapy was protective at borderline significance. After adjustment with a propensity score for recent chemotherapy, chemotherapy was not associated with outcome. CONCLUSIONS: Patients referred to the ICU with severe sepsis and septic shock complicating active chemotherapeutic treatment have better prognosis than commonly perceived.

Cutaneous mucormycosis as result of insulin administration in an AML patient: Case report and review of the literature.

We present a case of cutaneous mucormycosis in a patient with several important risk factors precipitating disease, namely underlying acute myeloid leukaemia and poorly controlled secondary diabetes. Inoculation was most likely caused by repeated minor trauma (insulin injection) at the site of infection. Treatment consisted of surgical debridement and liposomal Amphotericin B (LAmB) during 71 days. Posaconazole had already been initiated prior to infection as primary antifungal prophylaxis but was discontinued during follow-up as susceptibility testing later revealed resistance to posaconazole. Additional treatment with caspofungin and G-CSF was associated because of poor initial result to treatment. Caspofungin was later continued as monotherapy when LAmB had to be interrupted because of renal toxicity. Treatment was completed after closure of the surgical site. The patient was successfully treated and remains infection free for one year after initial diagnosis.

Aggressive extensive cardiac mass in an HIV-1-infected patient: should we go for comfort therapy?

Cardiac masses are rare, the differential diagnosis includes infections with vegetations or abscesses, neoplasms, thrombi, and structural abnormalities. A pathology specimen is essential in therapeutic strategy planning for a cardiac mass, also if the primary imaging findings look dramatic at the start. Even in an inoperable setting, a life-saving therapy might be available. We report a case of a 49-year-old man, known with HIV-1, who was several times admitted with pericarditis. Now he was hospitalized with progressive lower limb edema, atrial fibrillation and detection of a giant cardiac mass in left and right atrium with infiltration of surrounding tissues. Given the extent and invasiveness of the mass, he was inoperable. Biopsy specimen was obtained and staging was performed by PET-CT scan. The diagnosis of stage IV Burkitt lymphoma with predominant extranodal cardiac involvement was withheld wherefore promptly aggressive therapy was started according to the GMALL B-NHL86 protocol. The therapy was downgraded to R-CHOP due to tolerance problems. He achieved a complete remission and during follow-up no relapse was detected.

Impact of organ dysfunction on mortality in ICU patients with hematologic malignancies.

PURPOSE: To compare evolution in organ dysfunction (OD) between hematologic malignancy patients with and without bacterial infection (BI) precipitating intensive care unit (ICU) admission, and to assess its impact on mortality. METHODS: Retrospective analysis of prospectively collected data was performed. Sequential Organ Failure Assessment (SOFA) scores from day 1 to 5 were calculated in all consecutive hematologic malignancy patients admitted to the ICU (2000-2006). Patients were categorized according to the presence or absence, the diagnostic certainty, and the site of BI. RESULTS: Of the 344 patients admitted, 258 were still in the ICU at day 3 and 164 at day 5. Patients admitted because of BI had more severe OD on day 1 (SOFA 9.7 ± 4.0 vs. 8.4 ± 4.0, p = 0.008) but a more rapidly reversible OD within the first 3 days (ΔSOFA -1.12 ± 3.10 vs. 0.03 ± 3.40, p = 0.013) and a lower in-hospital (43.2% vs. 62.9%, p < 0.001) and 6-month mortality (52.1% vs. 71.7%, p < 0.001) than patients with other complications. In a multivariate analysis, BI remained associated with a lower risk of death (OR 0.20, 95% CI 0.1-0.4, p < 0.001) even after adjustment for the SOFA on day 1 (OR 1.36, 95% CI 1.22-1.52, p < 0.001) and the ΔSOFA (OR 1.48, 95% CI 1.29-1.68, p < 0.001). These findings remained significant regardless of the site and the diagnostic certainty of BI. CONCLUSION: BI is associated with a more severe initial but a more rapidly reversible OD and a subsequent lower mortality compared to other complications in ICU patients with hematologic malignancies. These findings further support the recommendation that these patients should certainly benefit from advanced life support, and in the case of an uncertain long-term prognosis due to the underlying malignancy, at least from a 3-day ICU trial.