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Purpose The main purpose of our study was to evaluate the ability of renal functional reserve (RFR) to stratify the risk of acute kidney injury (AKI) occurrence within 100 days of hematopoietic stem cell transplantation (HSCT) and to predict any functional recovery or the onset of chronic kidney disease (CKD). A secondary aim was to identify the clinical/laboratory risk factors for the occurrence of AKI. Patients and methods The study design is prospective observational. We enrolled 48 patients with normal basal glomerular filtration rate (bGFR) who underwent allogenic HSCT. A multiparameter assessment and the renal functional reserve test (RFR-T) using an oral protein load stress test were performed 15 days before the HSCT. Results Different RFRs corresponded to the same bGFR values. Of 48 patients, 29 (60%) developed AKI. Comparing the AKI group to the group that did not develop AKI, no statistically significant difference emerged in any characteristic related to demographic, clinical, or multiparameter assessment variables except for the eGFR. eGFR ≤100 ml/min/1.73 m2 was significantly related to the risk of developing AKI (Fisher exact test, p = 0.001). Moreover, RFR-T was lower in AKI+ patients vs. AKI- patients; but did not allow statistical significance (28% vs. 40%). In AKI patients, RFR > 20% was associated with complete functional recovery (one-sided Fisher extact test, p = 0.041). The risk of failure to recover increases significantly when RFR ≤ 20% (OR = 5.50, IC95% = 1.06-28.4). Conclusion RFR identifies subclinical functional deterioration conditions essential for post-AKI recovery. In our cohort of patients with no kidney disease (NKD), the degree of pre-HSCT eGFR is associated with AKI risk, and a reduction in pre-HSCT RFR above a threshold of 20% is related to complete renal functional recovery post-AKI. Identifying eGFR first and RFR second could help select patients who might benefit from changes in transplant management or early nephrological assessment.

The intravenous regimen of fludarabine plus cyclophosphamide (FC) at conventional doses is highly effective in Chronic lymphocytic leukemia (CLL), where it is currently indicated in first line therapy, and low-grade non Hodgkin lymphomas (LG-NHL). We have shown that intravenous or oral FC regimens at reduced doses remain highly effective in elderly patients with LG-NHL other than CLL. We tested tolerability and efficacy of oral FC at reduced doses in elderly patients with previously untreated (UT-CLL) or relapsed/refractory CLL (R-CLL). Twenty-five patients (>60 years) with UT-CLL (n=13) or R-CLL (n=12) were given oral F (25mg/m2/day, 40 mg total dose) and C (150mg/m2/day, 200 mg total dose) in an outpatient regimen for 4 consecutive days every 4 weeks for a maximum of 4 cycles. Patients were evaluated after every cycle for toxicity and hematological response. Toxicity was defined according to NCI criteria. Responses were defined as Complete (CR) when a normalization of blood count and misurable masses (lymph nodes and spleen) was documented, partial (PR) when at least a 50% reduction of lymphocytosis or nodes/splenomegaly occured, no response (NR) when disease was stable (less than PR) or progressed (>25% increment of tumor manifestations). Progression, new treatment or death was defined as “event”. Median age of the whole population was 70 years (range 61–80), 70 (61–80) in the UT-CLL, 71 (62–79) in the R-CLL. M:F distribution was 14:11 (7:6 in UT-CLL, 7:5 in R-CLL). Performance status was ≥1 in 80% patients. Of 25 patients, 16 (64%) were diagnosed CLL in stage A, 8 (32%) in stage B, 1 (4%) in stage C. Tumor IGHV gene was unmutated in 90% cases (in 85% UT-CLL, in 100% R-CLL). CD38 was positive in 68% (77% UT-CLL, 55% R-CLL) and ZAP-70 in 68% (82%, 67%). Chromosomal deletions of 11q or 17p regions were documented in 25.5% patients (27% UT-CLL, 25% R-CLL). The R-CLL had received 1–4 (median 2) treatment lines prior to FC. Median time from diagnosis or from prior treatment to FC was 24 months (range 1–77), 37 (1–77) in the UT-CLL, 12 (3–48) in the R-CLL. Overall, biological risk and clinical characteristics were indicative of an aggressive behavior of the investigated cohort. Patients received median 3 cycles (4 in UT-CLL, 3 in R-CLL). Nine-of-25 (36%) reduced the number of cycles because of fatigue (1 patient), heart failure (1), idiopathic thrombocytopenic purpura (1) in the UT-CLL (3/13) or infection (2), femur fracture (1), prolonged isolated thrombocytopenia or pancitopenia (2) and idiopathic thrombocytopenic purpura (1) in the R-CLL (6/12). Overall, 23/25 patients (92%) obtained a response (11/25 CR, 44%; 12/25 PR, 48%). Among UT-CLL, all responded to treatment (8/13 CR, 61.5%; 5/13 PR, 38.5%). Among R-CLL, 10/12 (83.5%) responded (3/12 CR, 25%; 7/12 PR, 58.5%; 2/12 NR, 16.5%). With a median follow-up of 23 months, 14/25 patients (56%) were event-free and 23/25 (92%) were alive. Among UT-CLL (median follow-up 12 months), 9/13 (69%) were event-free and all were alive. Among R-CLL (median follow-up 25 months), 5/12 (42%) were event-free and 10/12 (83%) were alive. Deaths occurred in the 2 R-CLL that had not responded to treatment, after 2 and 4 years, respectively. Despite the poor risk of the investigated population, this low-dose oral FC treatment showed good efficacy both in untreated and refractory/relapsed CLL. The treatment may be useful in elderly patients who cannot benefit of more aggressive or eradicating strategies and is easy to administer on an outpatient basis.