Acute myeloid leukemia of donor origin after allogeneic bone marrow transplantation for precursor T-cell acute lymphoblastic leukemia: case report and review of the literature

We report a case of donor-derived acute myeloid leukemia (AML) occurring in a 33-year-old man after allogeneic bone marrow transplantation (BMT) for precursor T-cell acute lymphoblastic -leukemia (T-ALL). The cells for BMT were from his human leukocyte antigen (HLA)-matched sister. Fluorescence in-situ hybridization (FISH) analysis showed the AML to be of donor origin (i.e., karyotypically female) with an 11q23 (mixed lineage leukemia (MLL) gene) translocation, while the original T-ALL exhibited a male karyotype with abnormalities of chromosomes 6, 8, and a t(10;14)(q24;q11.2). Subsequent molecular short tandem repeat studies confirmed the AML to be of donor origin. Donor-cell leukemia (DCL) after allogeneic BMT is a rare, yet well-documented, event. Our report presents clinicopathologic information about a case of DCL and a review of the recent literature.     

Therapy-related myelodysplastic syndrome of recipient origin after allogeneic bone marrow transplantation for acute lymphoblastic leukaemia

Therapy-related myelodysplastic syndrome (t-MDS) is a very rare complication of allogeneic bone marrow transplantation (BMT). A woman with T acute lymphoblastic leukaemia (T-ALL) received an allogeneic BMT from a donor with the beta-thalassaemic trait. Five years after BMT, the red cell indices returned to normal after an initial conversion to microcytosis, implying autologous haematopoietic regeneration. Seven years after BMT, thrombocytopenia developed and marrow examination confirmed t-MDS, with a characteristic karyotype 46,XX,inv(3)(q21;q26), del(5)(q13),add(17)(p11). Retrospective molecular analysis of donor/recipient chimaerism showed gradual regeneration of recipient cells after BMT, culminating at the time of t-MDS. Our findings illustrate the unusual occurrence of t-MDS after allogeneic BMT. Re-emergence of recipient haematopoesis may herald the development of a haematological malignancy different from the original neoplastic clone for which the BMT was performed.     

Improved outcome in adult acute myeloid leukemia is almost entirely restricted to young patients and associated with stem cell transplantation

Prognostic factors were studied in a series of 318 patients with acute myeloid leukemia (AML), 17-90 yr old, treated at a single centre during 1982-98, and representing 79% of the total number of cases registered in the area during this period. Risk group stratification based on cytogenetics, occurrence of antecedent hematological disorder, and leukocyte count could be performed in 93%. Five percent were allocated to the favourable risk group, 40% to standard risk, and 55% to adverse risk. Complete remission (CR) was attained in 52%. The CR rate was higher in the favourable (80%) and standard risk groups (69%) than in the adverse risk group (37%). The CR rate increased from 44% in the 1980s to 60% in the 1990s. The 5-yr survival rate for all patients was only 12%. Low age, promyelocytic leukaemia, treatment in the 1990s, high induction treatment intensity, and non-adverse risk group were favourably associated with survival. The median survival time increased from 115 to 349 d between the 1980s and the 1990s, but the 5-yr survival rate was only 11% for patients over 55 yr of age even in the last decade. For the younger patients, the 5-yr overall survival rate increased from 9% to 35% in the last decade. The median time in first remission was 365 d. Age below 56 yr, allogeneic and autologous transplants, and non-adverse risk group were associated with prolonged response duration. The duration of response among all patients increased from 250 d in the 1980s to 451 d in the 1990s, but event-free survival time did not improve significantly in patients above 55 yr of age. Among patients below 56 yr of age, overall survival and event-free survival were significantly better for those who received allogeneic or autologous transplants in first remission than for those who were treated with chemotherapy only. Overall survival times did not improve from the 1980s to the 1990s among those patients below 56 yr who were treated with chemotherapy only in first remission, in spite of the use of transplants in second remission.     

Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

Background

Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old.

Design and Methods

We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine.

Results

The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49–1.35) for survival and of 0.67 (95% CI, 0.42–1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22–1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22–1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40–3.42) and that for disease-free survival was 1.02 (99% CI, 0.40–2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65–2.27) for survival and 1.02 (95% CI, 0.56–1.85) for disease-free survival.

Conclusions

Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy. (Eudract number: NCT00002926; http://www.cancer.gov/clinicaltrials/EORTC-06961)     

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging for acute myeloid leukaemia beyond first remission: a 10-year experience

Between January 1987 and January 1997, 69 eligible patients with acute myeloid leukaemia (AML) in either second (CR2) or third (CR3) complete remission (CR2 = 60, CR3 = 9) underwent 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation (BMT) at the Johns Hopkins Oncology Center. The patients' median age was 27 years (range 1-62) and all received busulphan and cyclophosphamide as their preparative regimen. The probability of event-free survival (EFS) at 5 years was 30% [95% Confidence Interval (CI): 19-42%] for CR2 patients and 22% (3-51%) for those in CR3, with a median follow up of 8 years in the surviving group. The median time to an absolute neutrophil count of 0.5 x 109/l was 45 d (range 20-185). Relapse was the major cause of failure with a relapse rate of 55% in CR2 and 44% in CR3, while the non-relapse, transplant-related mortality rate was 15% in CR2 and 33% in CR3. In univariate analysis, patient age, cytogenetics, white blood cell count at presentation, CR1 duration and the sensitivity of clonogeneic leukaemia (CFU-L) in the graft to 4HC were all prognostic for EFS. Using each of these significant variables in multivariate modelling, patient age and sensitivity of CFU-L to 4HC were determined to be predictors of EFS. 4HC-purged autologous BMT produced results similar to allogeneic BMT for AML patients beyond first remission.     

非清髓异基因外周血造血干细胞移植治疗慢性粒细胞白血病

目的：探索非清髓异基因外周血干细胞移植(NST)治疗不能耐受清髓性异基因造血干细胞移植的慢性粒细胞白血病(CML)患者的疗效。方法：将5例CML患者中的4例以全身放疗加氟达拉宾，1例以马利兰、氟达拉宾加抗人胸腺细胞免疫球蛋白为预处理方案，联合环孢霉素A、霉酚酸酯和(或)短程氨甲蝶呤预防移植物抗宿主病。结果：5例均造血重建，3例完全供者型植入，2例混合型植入，其中1例植入率持续低于50％，经2次清髓性异基因造血干细胞移植后达到完全供者型植入。2例发生Ⅰ度急性移植物抗宿主病，1例发生Ⅳ度急性移植物抗宿主病，无慢性移植物抗宿主病发生。中位随访时间5(3～37)个月，无病生存3例，死亡2例。结论：对不能耐受清髓性异基因造血干细胞移植的CML患者，NST是可行而有效的。     

Autologous stem-cell transplantation for patients with acute myeloid leukemia aged over 60 yr

OBJECTIVES: Preliminary reports have suggested that autologous stem-cell transplantation (ASCT) is feasible in elderly patients with acute myeloid leukemia (AML). The objective of this study was to describe the disease characteristics and treatment results from a series of 22 elderly AML patients undergoing ASCT. METHODS: The median age was 64 yr (range 61-71). Twenty patients were in first complete remission (CR1), two in CR2, and all were in performance status 0-1. The median interval between CR achievement and ACST was 3 months (range 2-5). In 20 cases peripheral blood stem cells were infused, in two bone marrow. RESULTS: All patients had a successful engrafment. One patient (5%) died from transplant-related complications. The median number of days to granulocytes > 500 mm-3 and platelets > 20 000 mm-3 was 11(range 9-15) and 13 (range 9-20), respectively. Non-hematologic toxicity included WHO grade III-IV stomatitis in 32% patients and grade IV nausea and vomiting in one (4.5%). Seven patients had fever of unknown origin, while in 14 a documented infection was diagnosed. Median duration of hospitalization was 31 d (range 16-60). CONCLUSIONS: After a median follow-up of 12 months from ASCT, nine patients are alive in continuous CR and 13 died from AML relapse. Median survival from diagnosis and disease-free survival (DFS) was 19 and 14 months, respectively. Our data show that ASCT with a standard conditioning regimen is feasible in AML patients aged more than 60 yr. Toxicity and hemopoietic recovery do not substantially differ from those observed in young adults. DFS and overall survival (OS) duration are encouraging, but a longer follow up is needed on a larger series of patients.     

Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; >5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with >5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD4⁺ Th1 cells; these T cells expressed an exhaustion signature and were resistant to activation by T cell receptor stimulation in the presence of autologous AML cells. T cell activation could be restored by removing the AML cells or blocking the inhibitory major histocompatibility complex class II receptor, LAG3. Most LFR cases did not display these features, suggesting that their AML cells were not as immunosuppressive. These findings were confirmed and extended in an independent set of 50 AML cases representing all ELN 2017 risk groups. AML cell–mediated suppression of CD4⁺ T cell activation at presentation is strongly associated with unfavorable outcomes in AML patients treated with standard chemotherapy.

A normal karyotype (NK) is the most common cytogenetic finding in acute myeloid leukemia (AML) cells at presentation (NK-AML), and has long been associated with an intermediate risk for relapse (1). Although most NK-AML patients achieve a complete remission following standard induction chemotherapy (2, 3), the majority of patients experience relapse within 2 y, and fewer than 10% remain in remission beyond 5 y without an allogeneic transplant (4). Refinements introduced with the European LeukemiaNet (ELN) 2017 criteria (presence or absence of mutations in NPM1, FLT3-ITD, ASXL1, RUNX1, TP53, or biallelic CEBPA mutations) have helped to reclassify some NK-AML patients into the favorable- or adverse-risk group categories. However, the mutational heterogeneity of NK-AML, combined with our limited understanding of the biological consequences deriving from the interplay among mutations, still poses a major challenge for risk stratification at presentation, and for postremission treatment decisions (5, 6).The genetic and epigenetic characteristics of NK-AML patients with very long first remissions (LFRs) have not been defined, and it is not clear whether these patients are living free from disease, or whether they harbor “dormant” AML cells that may be held in check by immune surveillance or cell-intrinsic mechanisms. Predictive algorithms for identifying these very long responders at presentation do not yet exist, but clearance of all AML-associated mutations assessed after induction chemotherapy is strongly associated with prolonged relapse-free survival (RFS) and overall survival (OS) (7–12). Persistent ancestral clones have been detected in patients in complete morphologic remission within the first 2 to 3 y after treatment (13, 14), but similar studies of patients with very LFRs have not yet been described.Most published AML studies have justifiably focused on the mechanisms responsible for treatment failure. However, the reasons for chemotherapy successes are underexplored, even though they hold the potential to uncover determinants that are especially important for excellent outcomes that might be identifiable at presentation. To address this, we have studied two well-matched groups of NK-AML patients that were selected retrospectively for dramatically different outcomes after chemotherapy (long vs. standard first remissions, [SFRs]). In this study, we show that the outcomes of AML patients are not only related to their mutational status, but also to an immunosuppressive phenotype of AML cells at presentation (or lack thereof), a finding that was predicted 50 y ago by Freireich and colleagues (15) and extended in this report.     

Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors

Summary. Bone marrow transplantation from a histocompatible donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2–51, were treated withy high-dose chemoradiotherapy and transplantation of of 6/6 HLA matched ( n = 46) or one antigen mismatched ( n = 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17–24 months after transplant for a 2-year actuarial disease-free and overall survival of 23 ± 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 ± 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age >21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a sigbificant impact on survival with older age and adverse disease characteristics predicting for poor prognosis     

Localized relapse in bone marrow of extremities after allogeneic stem cell transplantation for acute lymphoblastic leukemia

We report a patient with a relapsed in bone marrow of extremities after allogeneic peripheral blood stem cell transplantation for acute lymphoblastic leukemia (ALL). The patient complained of pain in the right upper arm and left leg 15 months after transplantation. Magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal findings in bone marrow of upper and lower extremities. There were no findings of relapse in aspirates from the sternum and iliac bone marrow. Biopsy specimen from the iliac bone marrow showed normocellular marrow without leukemic cells. Biopsy specimen from the right humerus revealed marked leukemic cell infiltration in the bone marrow. This is apparently the first case of localized relapse of ALL in bone marrow of extremities. Physicians should be aware of unusual relapse sites of leukemia after allogeneic stem cell transplantation. MRI and FDG-PET may be of value in detecting this type of relapse.     

异基因造血干细胞移植治疗AML1/ETO(+)急性髓系白血病的疗效

目的:分析AML1/ETO(+)急性髓系白血病进行异基因造血干细胞移植后的临床疗效。方法:总结北京市道培医院2003年11月-2009年1月完成的24例AML1/ETO(+)急性髓系白血病患者进行异基因造血干细胞移植后的资料,使用Kaplan-Meier统计方法计算总体存活率、无白血病存活率和累积复发率,使用Logrank统计方法进行单因素分析。结果:24例患者移植后1年的总体存活率为(86.47±7.29)%,2年和3年的总体存活率为(69.00±10.77)%;移植后1年的无白血病存活率为(73.89±9.21)%,2年和3年的无白血病存活率为(67.17±10.54)%;移植后1、2年时的累积复发率分别为(27.75±8.09)%和(31.46±11.13)%。在单因素分析中,移植类型(同胞全合/单倍体/无关供者)、自确诊白血病到进行移植的时间间隔(12个月和12个月2组)、确诊时有无附加染色体异常、确诊时有无髓外浸润、确诊时的缓解状态(CR1和CR2/复发2组)等对总体存活率的影响均差异无统计学意义(均P0.05)。结论:异基因造血干细胞移植对AML1/ETO(+)急性髓系白血病患者具有良好疗效,是具有高危因素患者的治疗选择之一。     

Recombinant human granulocyte colony-stimulating factor (G-CSF) combined conditioning regimen for allogeneic bone marrow transplantation (BMT) in standard-risk myeloid leukemia

We previously suggested that using a combined conditioning regimen including rhG-CSF with allogeneic BMT in refractory AML and CML in blast crisis might reduce the rate of relapse and improve disease-free survival, without any major side effects. In this study, we used the same protocol for 10 AML patients in complete remission (CR) and 6 CML patients in the chronic phase (CP). We compared disease-free survival as well as toxic side effects of the regimen with 6 AML patients in CR and 6 CML patients in CP treated with chemoradiotherapy without G-CSF. The conditioning regimen consisted of TBI and high-dose AraC. RhG-CSF was infused continuously at a dose of 5 μg/kg/day, starting 24 hr before the initial dose of total body irradiation (TBI) until the end of AraC therapy. In all 28 cases, there were no early stage deaths due to regimen-related toxicity (RRT). None of the 10 AML cases treated with the G-CSF combined regime relapsed. In 6 AML cases treated conventionally without G-CSF, one patient died of infection and another relapsed. There were no relapses in either CML group. In the combined G-CSF group, one patient died of interstitial pneumonitis 48 days after BMT, while the rest of the CML cases are still alive. There were no relapses with rhG-CSF and no serious adverse effects in terms of RRT, acute graft vs. host disease (GVHD), or leukocyte recovery. Am. J. Hematol. 57:303–308, 1998. © 1998 Wiley-Liss, Inc.     

Allogeneic transplantation as post-remission therapy for cytogenetically high-risk acute myeloid leukemia: landmark analysis from a single prospective multicenter trial

Background Allogeneic hematopoietic cell transplantation is considered the preferred post-remission therapy in patients with acute myeloid leukemia cytogenetically defined as being at high risk. To substantiate evidence for allogeneic hematopoietic cell transplantation in first complete remission in these high-risk patients we performed a landmark analysis within a single prospective multicenter treatment trial. DESIGN AND METHODS: By the time of analysis, 2,347 patients had been accrued into the AMLCG 99 trial between 1999 - 2007. Out of this population, 243 patients under 60 years old fulfilled the criteria for high-risk cytogenetics. Landmark analyses were performed with a control cohort, who remained in first complete remission at least the median time from complete remission to transplantation in the intervention group. RESULTS: After standardized induction therapy, 111 patients under 60 years old achieved complete remission. A matched allogeneic donor was identified for 59 patients (30 sibling donors, 29 unrelated donors). Fifty-five patients received an allogeneic hematopoietic cell transplant after a median time of 88 days in first complete remission. Of the remaining 56 patients, 21 relapsed within 90 days after achieving first complete remission and for 7 patients with relevant comorbidities no donors search was initiated, leaving 28 patients given conventional post-remission therapy as the control cohort. The median follow-up of surviving patients was 60.4 months. Patients with an allogeneic donor had substantially better 5-year overall and relapse-free survival rates than the control group (48% versus 18%, P=0.004 and 39% versus 10%, P<0.001, respectively). A survival benefit from transplantation was evident regardless of donor type, age and monosomal karyotype. Conclusions Beyond evidence available for subgroups of high-risk patients, the findings of this study establish in a broader manner that allogeneic hematopoietic cell transplantation is a preferable consolidation treatment for patients with acute myeloid leukemia and high-risk cytogenetics. The study was registered at Clinicaltrials.gov as NCT00266136.     

Remission rate and survival in acute myeloid leukemia: impact of selection and chemotherapy

113 patients with acute myelogenous leukemia (AML), representing 82% of the total cohort of AML patients within the geographical area of northern Sweden, were recorded. The total complete remission (CR) rate was 47.8%, and median survival was 4 months. The probability of long-term survival for all patients without exclusions was only 5%. Thus, the results from this study differ strongly from data on patient outcome in most therapy studies in AML, where the influence of patient selection on the results is larger. The median age in our patients was 63 years, which is also higher than in most other studies. Elderly patients had a low CR rate (24% in patients greater than or equal to 70 yr), but remission duration was similar in the different age groups. Patients treated according to "high-dose" protocols had a CR rate of 64%, while only 14% of less aggressively treated patients achieved remission. A better response rate after more aggressive chemotherapy was evident also in elderly patients. CR rate was 81% in patients below 60 yr of age who had no antecedent blood disorder and who had had symptoms for less than 3 months. Other variables with prognostic implications were: cytogenetic subgroup, antecedent hematological disease, and level of serum ferritin. High serum ferritin was associated with short CR duration. Ferritin is produced by the leukemic cells and could be regarded as a marker for leukemic activity.     

Prognosis of acute myeloid leukemia harboring monosomal karyotype in patients treated with or without allogeneic hematopoietic cell transplantation after achieving complete remission

To evaluate the prognostic impact of monosomal karyotype on post-remission outcome in acute myeloid leukemia, we retrospectively analyzed 2,099 patients who had achieved complete remission. Monosomal karyotype was noted in 73 patients (4%). Of these, the probability of overall survival from first complete remission was 14% at four years, which was significantly lower than that reported in patients without monosomal karyotype, primarily due to a high relapse rate (86%). Monosomal karyotype remained significantly associated with worse overall survival among patients with unfavorable cytogenetics or complex karyotype, and even in patients who underwent allogeneic hematopoietic cell transplantation during first complete remission. These findings confirm that monosomal karyotype has a significantly adverse effect on post-remission outcome in patients with acute myeloid leukemia treated with and without allogeneic hematopoietic cell transplantation in first complete remission, emphasizing the need for the development of alternative therapies for this patient population.     

Results of risk‐adapted therapy in acute myeloid leukaemia. A long‐term population‐based follow‐up study

In 1997–2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18–60 yr were assigned to one of three risk groups. In this report we account for the long‐term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high‐dose cytarabine. Allogeneic stem cell transplantation (allo‐SCT) from an human leucocyte antigen‐identical sibling was recommended in standard and poor‐risk patients, whereas unrelated donor transplant was reserved for poor‐risk patients. Autologous (auto‐SCT) was optional for standard or poor risk patients not eligible for allo‐SCT. Two hundred seventy‐nine patients with de novo or secondary (9%) AML, median age 51 (18–60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard‐ and poor‐risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow‐up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4‐yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4‐yr OS rates were 60, 57 and 24%, respectively. Median relapse‐free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four‐year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred‐ten transplantations were performed in CR1; 74 allo‐SCT (50 sibling, 24 unrelated donor), and 36 auto‐SCT. Non‐relapse mortality was 16% for allo‐SCT patients. Outcome after relapse was poor with median time to death 163 d and 4‐yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population‐based cohort of adult AML patients <60 yr old; (ii) a risk‐adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.     

Natural effector cells in patients with acute myeloid leukemia treated with the immunomodulator Linomide after autologous bone marrow transplantation.

Roquinimex, Linomide, is a quinoline derivative with pleiotropic immunomodulatory activities which has been shown to enhance NK function. As part of a phase III placebo-controlled multicenter study patients were randomized to receive Roquinimex, 0.2 mg/kg body weight, or a placebo twice weekly for a duration of 2 yr following autologous bone marrow transplantation for acute myeloid leukemia in remission. At Arhus University Hospital 7 patients were randomized to receive the active drug and 6 to receive the placebo. Surviving patients were followed for 2 yr with immunological monitoring of their natural immune effector cells (NK- and LAK cell activity). Peripheral heparinized blood samples were obtained twice before the onset of conditioning therapy and at several time points after ABMT, and whole blood samples were analyzed by flow cytometry for the detection of leukocyte differentiation antigens as well as by 4 h 51Cr release assays for cytotoxicity. In contrast to previous experience with Linomide, in the present study we found that at 36 wk or later time points Linomide patients exhibited a significant suppression of circulating natural effector cell number and activity when compared with the control group. These observations underline the need for further exploration into novel and manageable immunostimulators.