Immunocompromised individuals such as chronic lymphocytic leukemia (CLL) patients are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate SARS-CoV-2-specific antibody responses in CLL patients, after the first, second and third doses of the BNT162b2 and mRNA-1273, and after a single dose for patients with confirmed prior COVID-19. Five hundred and thirty patients were included in the study. Patients received 2 doses at a 4-week interval, and a third dose if seronegative after the second dose. Response rate was 27% post-dose 1 and 52% post-dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients on therapy, patients on BTKi alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients on venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariate analysis identified as independent predictors of the absence of seroconversion: age >65 years, ongoing CLL treatment and gamma-globulins ≤6g/L. Post-dose 2 seronegative patients had a global post-dose 3 response rate of 35%. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

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Follicular lymphomas (FLs) are frequent B-cell derived malignancies, generally demonstrating an indolent evolution. Although circulating FL cells may be detected by high-resolution analysis, bloodstream involvement by FL cells is unusual. We observed in 10 patients a leukemic phase of FL at the onset of the disease. Six of them had concomitant lymph node involvement and all of them required treatment at diagnosis due to a high tumor burden, whereas four patients had pure FL-cell leukemia, which was associated with a more indolent clinical outcome. The detection of a leukemic phase should therefore be studied as a potential prognosis marker in further studies.

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Only few elderly ALL patients are entered to prospective trials and the data on patient characteristics and outcome are scarce. The European Working Group for Adult ALL (EWALL), which was funded in 2001 by all major national European study groups for adult ALL, therefore focused on the development of rational treatment approaches for elderly ALL as an unmet medical need. The group agreed on a chemotherapy backbone mainly based on elements derived from previous French and German protocols for elderly ALL. After a pre-phase with dexamethasone +/− cyclophosphamide the 4-week-induction comprised dexamethasone (10 mg/m2, d1–2,8–11), vincristine (1 mg, d 1,8), idarubicine (10 mg, d 1–2,8–9) in phase I and cyclophosphamide (500 mg/m2, d15–17) and cytarabine (60 mg/m2, d16–19, 23–26) in phase II. Consolidation consisted of 6 alternating cycles with 3 times methotrexate (1000 mg/m2, d1) and E.coli asparaginase (10000 U/m², d2) and 3 times high-dose cytarabine (1000 mg/m2/q12 hrs, d1,3,5) followed by maintenance with mercaptopurine, methotrexate and vincristine/dexamethasone pulses for a total treatment duration of 2 yrs. Dose reductions were recommended for pts older than 70 yrs, and slight modifications were made in the three participating countries. In a separate protocol the backbone chemotherapy is used in combination with Dasatinib for pts with Ph/BCR-ABL+ ALL. Between 1/07 and 8/08 54 pts with Ph-negative ALL from 33 centers were treated, and 40 pts were evaluable for response after induction (France 20, Germany 13 and Spain 7). The median age was 66 (56–73) yrs with 22% older than 70 yrs. General condition (ECOG) was 2–3 in 23%. 65% had c/pre-B-ALL, 15% pro-B, 17% T-lineage and 1 pt biphenotypic ALL. Cytogenetics (N=30) were normal in 40%, t(4;11) in 7%, complex in 7% and with other aberrations in 47%. 23% had WBC above 30000/μl at diagnosis. 34 (85%) pts achieved CR after induction. PR or failure was observed in 7% resp. No pt died during induction. 85% of the pts were alive at a median follow-up of 8 mo. The probability of survival after 1 year is 61%. 4/34 CR pts were withdrawn in CR from further treatment (12%). Of the remaining 30 CR pts 23 are in CCR (77%), 1 died in CR due to fungal septicaemia (3%), 6 relapsed (20%). The probability of continuous CR after 1 year is 49% with a median remission duration of 9 mo. During induction I and II the majority of pts experienced grade III–IV adverse events (AE), most frequently cytopenias (>90%) and infections (16% phase I, 25% phase II). Treatment with HDMTX/ASP (Cons I or III) was evaluable in 44 cycles. 45% were associated with grade III–IV AE, most frequently cytopenias, infections, liver disturbance and allergy to asparaginase in 2 pts. HDAC (Cons II or IV) was evaluable in 34 cycles with 47% grade III–IV AEs, again mostly cytopenias. With this age adapted induction regimen for elderly pts (median age: 66 yrs) a high CR rate (85%) was achieved. The moderate intensity consolidation treatment was tolerable, and the low rate of treatment related death elucidates the fact that intensive supportive treatment e.g prophylaxis/treatment of infections can be successful in elderly pts. It is noteworthy that treatment with asparaginase as a major drug for ALL, which was so far rarely used in elderly pts, was feasible as well. Although follow-up is short, the survival probability of 61% after 1 year is promising. In future trials new investigational drugs will be added to the backbone in order to evaluate their efficacy and feasibility in randomised studies. Partly supported by the European Union (European Leukemia Net)

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