Vaccination coverage in hematological patients undergoing chemotherapy: Should we move towards personalized vaccination?

INTRODUCTION: Immunocompromised patients are at high-risk for severe influenza and invasive pneumococcal diseases (IPD). Despite the French Public Health Council (FPHC) and the 7th European Conference on Infections in Leukaemia (ECIL7) recommendations, vaccination coverage remains insufficient. This study aimed to estimate the coverage and determinants of influenza, pneumococcal and diphtheria-tetanus-poliomyelitis (dTP) vaccinations in hematological patients underlying chemotherapy. METHODS: A survey was distributed to all patients of the hematology day hospital assessing vaccine uptakes and general opinion about vaccination. Vaccine uptakes were collected from medical and vaccination records; knowledge of and attitudes towards vaccinations in immunocompromised patients were evaluated for each general practitioner (GP) by phone call. Adequacy between vaccine uptakes and indication or not to vaccinate according to ECIL7 guidelines was assessed. Factors associated with vaccine uptakes were assessed by multivariate logistic regression. RESULTS: Among 145 patients, 66 % were aged 65 years or older, 40 % were followed for lymphoma and 38 % for multiple myeloma, 39 % were treated with anti-CD20 antibodies. Vaccination coverage was suboptimal for influenza (45-56 %), dTP (44 %) and IPD (16-19 %) regardless of the guidelines followed, with a wide variation in rates by information source (19-76 %). Adequacy rate with ECIL7 recommendations were 63 % and 87 % for influenza and IPD respectively. Information of patients on specific vaccinations was positively associated with flu and IPD vaccinations, as well as favorable attitude toward vaccination and age ≥ 65 years for flu vaccination, and recommendation by hematologist for pneumococcal vaccination. CONCLUSION: Despite vaccination opportunities, the complexity of these specific recommendations and the lack of communication between the health actors could explain the suboptimal vaccination coverage in this high-risk population. A proactive attitude of all actors in the city and hospital, including better patient information and a personalized and evolving vaccination schedule to help GPs to coordinate vaccination would allow to improve vaccine coverage.

Hematopoietic stem cell transplantation with unrelated cord blood or haploidentical donor grafts in adult patients with secondary acute myeloid leukemia, a comparative study from Eurocord and the ALWP EBMT.

Survival of patients with secondary acute myeloid leukemia (sAML) is poor. Cord blood transplantation (UCBT) and non-T-cell-depleted stem cell transplantation from haploidentical donors (HAPLO) are both strategies that have shown encouraging results in patients who do not have an human leukocyte antigen (HLA)-matched sibling or unrelated donor. We retrospectively analyzed outcomes of 409 adults with sAML receiving either UCBT (n = 163) or HAPLO (n = 246) in EBMT centers. Myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) was the antecedent diagnosis in 79% of UCBT and 85% of HAPLO recipients. In multivariate analysis, UCBT was associated with higher risk of grade II-IV acute GVHD (HR 1.9, p = 0.009) and lower GHVD-free-relapse-free-survival (GRFS) (HR 1.57, p = 0.007) compared to HAPLO. Chronic-GVHD, RI, NRM, LFS, and OS were not statistically different between the two. Early disease stage at transplant was independently associated with lower RI and NRM and higher OS and LFS. These results indicate that HAPLO is associated with better GRFS and lower aGvHD compared to UCBT in patients with sAML and that UCBT can be a valid alternative for sAML patients who lack a matched sibling, a proper haploidentical or an unrelated donor.

Long-term follow-up of European APL 2000 trial, evaluating the role of cytarabine combined with ATRA and Daunorubicin in the treatment of nonelderly APL patients.

All-trans retinoic acid (ATRA) combined to anthracycline-based chemotherapy is the reference treatment of acute promyelocytic leukemia (APL). Whereas, in high-risk patients, cytarabine (AraC) is often considered useful in combination with anthracycline to prevent relapse, its usefulness in standard-risk APL is uncertain. In APL 2000 trial, patients with standard-risk APL [i.e., with baseline white blood cell (WBC) count <10,000/mm(3) ] were randomized between treatment with ATRA with Daunorubicin (DNR) and AraC (AraC group) and ATRA with DNR but without AraC (no AraC group). All patients subsequently received combined maintenance treatment. The trial had been prematurely terminated due to significantly more relapses in the no AraC group (J Clin Oncol, (24) 2006, 5703-10), but follow-up was still relatively short. With long-term follow-up (median 103 months), the 7-year cumulative incidence of relapses was 28.6% in the no AraC group, compared to 12.9% in the AraC group (P = 0.0065). In standard-risk APL, at least when the anthracycline used is DNR, avoiding AraC may lead to an increased risk of relapse suggesting that the need for AraC is regimen-dependent.

Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience.

PURPOSE: Acute promyelocytic leukemia (APL) with pretreatment WBC counts greater than 10,000/microL is still considered to carry a poorer prognosis than APL with WBC lower than 10,000/mL. We evaluated outcome improvement in such patients in recent years. PATIENTS AND METHODS: Nine hundred two patients with APL, including 204 patients and 68 patients with WBC counts more than 10,000/microL and more than 50,000/microL, respectively, were enrolled between 1993 and 2005 in two successive randomized trials of the European APL group (APL 93 and APL 2000) that tested, in particular, the modalities of combination of all-trans retinoic acid (ATRA) and chemotherapy, maintenance treatment, escalating doses of cytarabine, early administration of dexamethasone, and CNS prophylaxis. RESULTS: Between the APL 93 and 2000 trials, the complete response (CR) rate increased from 89.6% to 93%, and the 5-year cumulative incidence of relapse (CIR) decreased from 40% to 9.5% in patients with WBC counts of 10,000 to 50,000/microL. In patients with WBC counts more than 50,000/microL, the CR rate increased from 82% to 91%, and 5-year CIR decreased from 59% to 24%. Whereas in the APL 93 trial, increased WBC counts were significantly associated with higher CIR and shorter survival, this was not the case in the APL 2000 trial. In patients with increased WBC counts, enrollment onto the APL 2000 trial (v APL 93) and combined maintenance with ATRA and chemotherapy were associated with significantly lower CIR and better survival. CONCLUSION: Outcome of APL with high WBC count has markedly improved over the years as a result of fewer early deaths and fewer relapses. Better initial supportive care and combined maintenance treatment have contributed to this improvement.