Background: At present, no other therapeutic strategy has substantially outperformed purine nucleoside analogues (PNAs)—introduced around the late 1980s and early 1990s—to manage hairy cell leukemia (HCL). The most recent population-based study in HCL showed that 10-year relative survival of HCL patients diagnosed in the Netherlands during 2001-2015 was 97%, 95%, and 83% in the age groups <60, 60-69, and ≥70 years, respectively (Dinmohamed AG et al. Blood; 2018). Given the improved longevity of HCL patients, relative survival rates fall short to inform on longevity across the entire patients’ life span. Aims: Studies estimating the life expectancy of HCL patients are hitherto lacking. Therefore, we assessed trends in the life expectancy of HCL patients from a historical and contemporary perspective. Methods: We selected all HCL patients diagnosed between 1989 and 2019—with follow-up for survival up to January 1, 2021—from the Netherlands Cancer Registry (N=1,828; median age, 60 years; interquartile range, 50-70 years; 78% males). We estimated the loss in expectation of life (LEL)—i.e., the difference between the life expectancy of patients and an age-, sex-, and period-matched group from the general population—using flexible parametric relative survival models. The LEL is interpreted as the average number of life years lost due to an HCL diagnosis. The LEL can vary markedly across ages because life expectancy is age-dependent. Therefore, the proportional LEL (PLEL) was estimated. These survival measures were presented by year of diagnosis for four ages at diagnosis (i.e., 40, 50, 60, and 70 years), stratified by sex. Results: The life expectancy of HCL patients increased gradually across all ages between 1989-2019, irrespective of sex (Fig A). It is noteworthy that HCL patients diagnosed in 1990 lost comparatively few life-years due to their diagnosis, ranging from a LEL of 1.7 to 3.9 life-years lost depending on age and sex (Fig B). Estimates for patients diagnosed in 2019 ranged from 0.8 to 1.9 life-years lost (Fig B). Over time, the decrease in LEL was most pronounced for younger patients (Fig B). For example, a 50-year-old male diagnosed with HCL in 1990, on average, has a LEL of 3.8 years (95% confidence interval [CI]: 2.1-5.5), whereas a male with a HCL diagnosis in 2019, on average, has a LEL of 1.0 years (95% CI, 0.3-1.7). The corresponding estimates for a 70-year-old male HCL patient were 2.3 (95% CI, 1.4-3.1) and 1.1 (95% CI, 0.6-1.7), respectively. The PLEL estimates also portrays that outcomes in HCL patients improved over time across all ages (Fig C). Nevertheless, there was a persistent age differential in the PLEL over time. More specifically, younger patients consistently have more remaining life-years than older patients, reflected in lower PLEL estimates in younger patients. Of note, the life expectancy estimates of female patients should be interpreted with caution by considering the wideness of the 95% CIs due to the comparative rarity of HCL in females to estimate the life expectancy accurately. Image:Summary/Conclusion: The life expectancy of HCL patients verges upon the life expectancy of the general population. This encouraging finding was already objectified around the early-1990s when PNA therapy was introduced for HCL management. Thereafter, the life expectancy gradually increased over time. Novel therapeutic strategies may reduce the minimal excess mortality encountered in contemporary diagnosed patients, particularly among the elderly.

In this study we analyzed 40 patients with AML who received donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT). Patients with a median age of 42 (range, 11–66) were transplanted with an in vitro T-cell depleted (Campath in the bag) graft from an HLA matched sibling following a myeloablative (n=35) or a nonmyeloablative conditioning regimen (n=5). Patients received DLI for relapsed AML (n=28) or for mixed chimerism (n=12). All patients with relapsed AML were treated with a cytarabine-containing chemotherapy regimen or with gemtuzumab ozogamycin immediately prior to DLI treatment and received daily 3 x 10 6 U α-IFN sc. The DLI dose administered was depending on the protocol used. Fourteen relapsed patients received high dose DLI with a median of 50 x 10 6 CD3 + cells/kg and 14 low dose DLI with a median of 5 x 10 6 CD3+ cells/kg. Ten of 28 patients with relapsed AML obtained a complete remission after the combination of chemotherapy and DLI. One patient obtained a partial remission and fourteen patients showed no response. Three patients were not evaluable. No effect of cell dose was observed on the clinical response after DLI. The median percentage of donor chimerism in patients with relapsed AML before DLI was 74% (range, 5–96%) and increased after DLI to 97% (range, 5–100%). Six patients with relapsed AML became complete chimera after DLI. DLI caused in 12 of 28 relapsed patients grade 3–4 GVHD. cGVHD was observed in 3 patients of whom 2 developed extensive GVHD. With a median follow up of 11 months only 1 pt in the high dose and 4 pts in the low dose group are alive in CR and 23 have died due to progressive disease (16) or GVHD (7). Due to this low rate of long-term survival of relapsed AML patients treated with DLI, we recently developed a new DLI protocol for AML patients. Twelve patients with mixed chimerism at 6 months after T-cell depleted alloSCT were pre-emptively treated with 3 x 10 6 CD3 + cells/kg. Complete chimeric response was observed in 6 of these 12 patients. Two patients showed increasing mixed chimerism and three patients showed no response. Two of 12 patients treated for mixed chimerism developed aGVHD gr 1–2. No severe aGVHD was observed in this group. Two patients developed chronic GVHD, both after nonmyeloablative conditioning. Incidence of GVHD was significantly lower in this group compared to the relapsed patients. Currently, 7 patients are alive in CR. In conclusion: 1) Long term survival of patients with overt relapse AML after alloSCT treated with DLI remains poor 2) High dose DLI appeared to be less effective than low dose DLI due to increased toxicity 3) DLI for AML may be more successful when it is administered pre-emptively for mixed chimerism after T-cell depleted alloSCT.

Transplantation of stem cells that are T-cell depleted using Campath 1H incubation following non-myeloablative (NM-alloSCT) conditioning leads to durable donor engraftment with minimal GVHD using HLA-identical family sibling and unrelated donors. The high levels of donor chimerism allow the subsequent use of DLI to treat residual disease (Exp. Hematol. 2003; 31: 865–872). Patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) have a short life expectancy. We analyzed 12 patients with advanced CLL (9), PLL (1) or M. Waldenstrom (2) treated with NM-alloSCT. Median age was 56 years. Recipient conditioning consisted of fludarabine (30 mg/m2, 6 days), ATG (10 mg/kg, 4 days) and busulphan (3.2 mg/kg, 2 days). High numbers of G-CSF mobilized peripheral blood CD34+ cells from 11 related and 1 unrelated donors were collected (median 12 x 106/kg). The graft was T-cell depleted by 30 minutes incubation with 20 mg Campath 1H. No post-transplant GVHD prophylaxis was administered. The transplant procedure was very well tolerated. All patients engrafted rapidly. Only 1 patient experienced GVHD gr I (skin) after alloSCT. Sequential chimerism studies of bone marrow showed sustained mixed chimerism with a median donor percentage at 3 months after alloSCT of 86% (range 8–100%). At a fixed time period of 6 months after NM-alloSCT, low dose DLI was administered (5 x 106 CD3+ cells/kg) in 8 patients (3 pts too early after alloSCT and one pt died before DLI). The disease status pre-DLI was persistent disease in 4 pts and CR in 4 pts. After DLI, four patients experienced severe aGVHD (≥ grade 2) and 1 limited cGVHD. Importantly, the observed GVHD after low dose DLI was well managable. One patient received a second transplant from the original donor after myeloablative conditioning due to progressive disease with concommitant decreasing mixed chimerism. Donor chimerism increased after DLI with a median donor percentage of 98% (range, 3–100%) at 3 months after DLI. Presently at a median follow-up of 423 (range 46–1572) days, 9 patients are alive. Four patients are in complete remission, 3 with partial remission and 2 with progressive disease. Three patients have died, two due to infection and one by unknown cause.