Acute myeloid leukemia in patients we judge as being older and/or unfit

Definition of older age in AML is arbitrary. In the context of the clinical studies, it starts with age ≥ 60 or ≥65 years and in recent years ≥70 or 75, depending on the selection of the studied population. In clinical practice, with older age we often mean that the patient is unfit for intensive chemotherapy. Higher age overlaps with categories such as worse performance status, unfitness, co-morbidities, poor-risk cytogenetics, adverse mutation patterns, age-related clonal hematopoiesis and specific disease ontogeny. Intensive induction therapy can result in prolonged overall survival, at least in a subset of elderly patients aged up to 75 years despite the reluctance of some physicians and patients to use treatment regimens perceived as toxic. Venetoclax and azacytidine combination is the new standard of comparison for persons unfit for intensive therapy. New oral hypomethylating agent CC-486 as maintenance therapy led to a prolonged overall survival in a randomized trial of patients ≥ 55 years or age who were in first complete remission, not eligible for allogeneic stem cell transplantation. Any therapy is better than no therapy, but a substantial proportion of older patients still receive only palliative care. Making a decision for AML diagnosed in older age should be individualized and shared through the dialog with the patient and relatives or cohabitants, considering medical issues as well as social factors including personal goals. Although we are witnesses of the advances in basic research and therapy, we are still a very long way from curing older patients with AML

Mutational spectrum of de novo NPM1-mutated acute myeloid leukemia patients older than 75 years

AML with mutated NPM1 occurs in all age groups. Yet, the mutational pattern is not extensively studied in the very old, which may hamper appropriate risk assessment. Herein we examined 22 cases of NPM1-mutated de novo AML in patients older than 75, with a median age of 84. All diagnostic samples were sequenced aiming for coverage of the most relevant AML-associated mutations. For comparison with younger patients, we used already published data on several cohorts. A total of 76 mutations including 50 different variants were identified in 16 recurrently mutated AML genes. Compared with younger patients, a significant enrichment of TET2 and SRSF2 was observed, together with a reduced frequency of DNMT3A mutations. Our results indicate that the mutational pattern may be different in the very old as compared to younger patients with NPM1-mutated AML.HighlightsThe mutational spectrum of NPM1-mutated AML in patients above 75 years displays distinct features.A significant enrichment of TET2 and SRSF2 mutations together with a reduced frequency of DNMT3A mutations was observed in the elderly.NPM1 mutation is a secondary event in the development of AML in the very old

Relatively favorable outcome after allogeneic stem cell transplantation for BCR-ABL1-positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

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An investigation into whether deletions in 9p reflect prognosis in adult precursor B-cell acute lymphoblastic leukemia : a multi-center study of 381 patients

In acute lymphoblastic leukemia, besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important prognostic markers and are often included in the treatment stratification of patients with adult acute lymphoblastic leukemia. Deletions in 9p are seen in about 9% of cases of adult acute lymphoblastic leukemia, but their prognostic impact has been controversial. Cytogenetic data from 381 patients diagnosed with B-precursor acute lymphoblastic leukemia were reviewed. Chromosomal analysis was successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they were compared with patients with normal karyotypes and patients with t(9;22)/BCR-ABL. Patients with abnormalities of chromosome 9 showed significantly shorter overall survival compared with patients with normal karyotypes. In fact, overall survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive group. Our data suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor acute lymphoblastic leukemia

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory GI Acute GvHD : A Retrospective Record Review

Allogeneic hematopoietic cell transplantation can be curative in patients with hematological malignancies but carries a significant risk of graft-versus-host disease (GvHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GvHD (aGvHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treatment of SR GI aGvHD. Data from medical records of patients were collected, and criteria for extraction included: no more than 1 allogeneic hematopoietic cell transplantation and at least 1 dose of vedolizumab as treatment for SR GI aGvHD (stage I-IV GI aGvHD following ≥1 previous treatment regimen containing ≥1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites and had received 1-10 doses of IV vedolizumab 300 mg (median 3 doses) as treatment for SR GI aGvHD. The overall response rate at 6-10 weeks after vedolizumab initiation was 64% and OS at 6 months was 54%. There were 29 SAEs including 12 infections; 3 SAEs were considered possibly related to vedolizumab (2 of which were infections). Thirteen SAEs were fatal, 1 of which was possibly vedolizumab-related. There were 8 non-serious infections with confirmed GI origin and 1 serious (in 8 patients); there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting are required from prospective trials

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden : graft-versus-leukemia effect protects against relapse

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT