Allogeneic hematopoietic cell transplant following crizotinib monotherapy for relapsed/refractory anaplastic large cell lymphoma

Abstract

Relapsed ALK-positive ALCL often is responsive to CRZ monotherapy. The subsequent role of allogeneic HCT after achieving second remission is poorly understood. We report 6 children who underwent allogeneic HCT for relapsed ALCL after CRZ. Age at transplant ranged from 10.7 to 22.6 years. Follow-up ranged from 0.9 to 4.5 years. All patients engrafted. Three of 4 patients that received a reduced-toxicity conditioning regimen containing fludarabine, alemtuzumab, and low-dose irradiation showed progressive mixed chimerism. Five patients remain in remission. One patient developed isolated CNS relapse 3.6 years after HCT despite a lack of previous CNS involvement. No acute transplant-related complications were experienced. One patient developed chronic renal disease secondary to transplant-associated microangiopathy and one patient chronic GVHD secondary to DLI. Ultimately, allogeneic HCT appears safe and potentially curative after remission induction with CRZ. The role of conditioning therapy, ablative or reduced intensity, remains uncertain for patients' post-CRZ monotherapy, and further studies may be warranted.

Second allogeneic transplantation using umbilical cord blood for a patient with relapsed ALK+ anaplastic large cell lymphoma after allogeneic bone marrow transplantation in the era of ALK inhibitors

“…Tami et al showed an excellent outcome of an allogeneic HSCT in relapsed/refractory ALK+ ALCL after crizotinib with long-term remission in 5 out of 6 patients. [ 6 ] The same group and others reported favorable outcomes of allogeneic HSCT in relapsed/refractory ALCL patients suggesting a graft-versus-lymphoma (GVL) effect. [ 19 – 21 ] Although the optimal treatment for chemotherapy-resistant ALK+ ALCL patients has not been established yet, so far it seems to be a reasonable option to use novel agents to achieve remission and undergo allogeneic HSCT as soon as possible.…”

“…[ 1 ] However, in an extremely rare subset of patients (3–4%), ALK+ ALCL with leukemic presentations is known to be chemotherapy-resistant. [ 1 – 3 ] Novel therapies, such as Brentuximab Vedotin (BV), [ 4 , 5 ] which is an anti-CD30 monoclonal antibody conjugated with monomethyl auristatin E, and ALK inhibitors, [ 6 – 11 ] have been tested for relapsed/refractory ALK+ ALCL. Also, high dose chemotherapy followed by autologous stem cell transplantation or allogeneic hematopoietic stem cell transplantation (HSCT) have shown long-term benefits for these patients.…”

Refractory Anaplastic Large Cell Lymphoma Rescued by the Combination of the Second-Generation ALK Inhibitor Brigatinib, High-dose Chemotherapy and Allogeneic Stem Cell Transplantation: A Case Report and Review of the Literature

“…In a series of 6 R/R ALCL patients who underwent allogeneic HSCT after obtaining a complete clinical and radiological remission with crizotinib monotherapy, 3 of 4 who were conditioned with a RIC presented mixed chimerism which required repeated donor lymphocyte infusions. One of these patients reverted to full-donor chimera but developed extensive chronic GVHD, while one of the other two patients relapsed on the CNS 3.6 years after HSCT and died [29].…”

Traditional and emerging therapies for anaplastic large cell lymphoma (Review)

“…Several case reports also reported that crizotinib alone or combined with HSCT had a good therapeutic effect in R/R ALCL (69)(70)(71)(72)(73)(74). Alitinib, a second-generation ALK inhibitor, has also been reported to induce CR in patients with ALK + ALCL (75).…”