Survival of early posthematopoietic stem cell transplantation relapse of myeloid malignancies

Abstract

Objective: Relapse of AML after allogeneic hematopoietic stem cell transplantation (HSCT) has a poor prognosis, and standard of care therapy is lacking. Early (<6 months) relapse is associated with dismal outcome, while the majority of relapses occur early after transplantation. A more precise indication which patients could benefit from reinduction therapy is warranted. Methods:We retrospectively analyzed outcomes of 83 patients with postallogeneic HSCT relapse. Patients were divided based on intention to treat (curative vs supportive care). Results:Of the 50 patients treated with curative intent, 44% reached complete remission (CR) upon reinduction chemotherapy, and of these patients, 50% survived.Two survivors reached CR after immunotherapy (donor lymphocyte infusion (DLI), without reinduction chemotherapy). Sixty-nine percent of the survivors had received high-intensity cytarabine treatment, followed by immunologic consolidation. Relapse <3 months after transplantation was predictive for adverse survival (P = .004), but relapse <6 months was not. In fact, >50% of the survivors had a relapse <6 months. Conclusion:We confirmed the dismal prognosis of postallogeneic HSCT relapse.Importantly, our data demonstrate that patients fit enough to receive high-dose chemotherapy, even when relapse occurred <6 months, had the best chance to obtain durable remissions, in particular when immunologic consolidation was performed after reaching CR. K E Y W O R D S acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, graft-versusleukemia, outcome Allogeneic hematopoietic stem cell transplantation (HSCT) is the preferred treatment for patients with (MRD positive) intermediate-risk or poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). While transplant related mortality has decreased, the risk for relapse has not. Disease relapse is a common and important cause of the poor long-term survival of allogeneic HSCT recipients with AML. Relapse accounts for 30%-40% of deaths after allogeneic HSCT, depending on the type of the donor and disease status at transplant. 1,2 Prognosis of postallogeneic HSCT AML relapse is poor 3,4 and has hardly improved in the past decades. There is no standard of care for patients who relapse after allogeneic HSCT. Age (<37 year) and a longer time (>5 months) between allogeneic HSCT and relapse have been identified as favorable prognostic factors. 3,5,6 Other factors such as clinical condition and personal considerations of the patient may be weighed in the decision to either give supportive care, offer low-dose chemotherapy, or attempt high-dose reinduction chemotherapy. In reality, curative treatment options are often limited, and in many cases, it can be more appropriate to refrain from intensive treatment regimens and opt for best supportive care. Most AML relapses occur in the first 6 months after allogeneic HSCT, a period during which many patients still receive immunosuppressive therapy. Rapid tapering of immunosuppression can potentially lead ...

Conditioning therapy with N‐acetyl‐L‐cysteine, decitabine and modified BUCY regimen for myeloid malignancies patients prior to allogeneic hematopoietic stem cell transplantation

“…For patients with higher risk factors (adverse cytogenetic, ≥3 molecular‐genetic abnormalities, partial response or non‐response prior HSCT), the cumulative incidence of relapse is 35% (95% CI 0.18–0.60) in Arm A, and 52.0% (95% CI 0.34–0.72) of Arm B ( p = .333) (Figure 2B). One patient in Arm A (11.1%) experienced an early relapse (relapse within 3 months after HSCT), 23 and nine patients in Arm B (47.4%) ( p = .098). Relapse related‐mortality was 44.4% and 66.7% in 2 arms, respectively.…”

T cell optimization for graft-versus-leukemia responses

“…Long-term survival after post-HCT relapse is infrequent. Reported 2-year overall survival (OS) in patients relapsing at less than 3 months, 3-6 months, and greater than 6 months is 3%, 9%, and 19%, respectively, while average survival after post-HCT relapse is 4 months (17)(18)(19)(20). More options now exist to treat post-HCT relapse, including CD19 chimeric antigen receptor (CAR) T cells for patients with B lineage acute lymphoblastic leukemia (ALL) and hypomethylating agents for patients with acute myeloid light blue indicates early post-HCT risks primarily related to conditioning, darker blue indicates later post-HCT risks related primarily to immunosuppression and GVHD.…”

Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse

“…1,2 Available therapeutic options include donor lymphocyte infusions, hypomethylating agents alone or in combination, chemotherapy, and a second allograft, but long-term benefit is usually limited to those who are eligible for a second immune cellbased intervention. 1,[3][4][5] Natural killer (NK) cells eliminate cancer cells through the release of cytotoxic granules triggered by interactions with natural ligands or through FcgRIIIA/CD16-mediated recognition of antibody-decorated cells, in a process called antibody-dependent cellular cytotoxicity (ADCC). 6 The cytokines of the common g-chain family interleukin-2 (IL-2) and IL-15 endow NK cells with improved effector functions and extend their persistence in vivo.…”