Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

Wang, Dongmei; Shi, Rui; Wang, Qinglong; Li, Jianqiang

doi:10.2147/ott.s164430

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…The 1 patient with testicular relapse underwent orchiectomy before infusion of tisagenlecleucel and had no measurable disease in his BM. Trafficking of the CAR-T cells was not directly analyzed in this patient; however, CAR-T therapy has been shown to reach non-CNS sites of EM disease, such as the cervix, breast, and bone, as well as testes [16][17][18][19], and this patient did have grade 1 CRS, suggesting possible CAR-T-mediated effects.…”

Section: Discussionmentioning

confidence: 94%

Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia

Rubinstein

Krupski

Nelson

et al. 2020

Biology of Blood and Marrow Transplantation

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Autologous CD19-directed chimeric antigen receptor T lymphocyte (CAR-T) therapy is an approved and effective treatment for the management of patients with refractory and multiply relapsed B cell precursor acute lymphoblastic leukemia (B-ALL). Experience using this therapy in pediatric patients with extramedullary (EM) disease is limited, in part because these patients have frequently been excluded from clinical trials owing to concerns for an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS). We infused 7 patients with refractory or multiply relapsed B-ALL who presented with isolated EM relapse with tisagenlecleucel. Six patients had isolated central nervous system (CNS) leukemia, and 1 patient had an isolated testicular relapse. An initial complete response was seen in all patients, with 5 patients remaining in CAR-T-induced remission at a median of 18 months from first infusion. Reversible ICANS was seen in 1 patient with CNS leukemia. Durable B cell aplasia occurred in 3 patients, with a median time to B cell recovery of 6.5 months in the other patients. These data suggest that CAR-T therapy has promising safety and efficacy in treating EM leukemia, although definitive conclusions are limited by the small size of the cohort and limited follow-up period.

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Section: Discussionmentioning

confidence: 94%

Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia

Rubinstein

Krupski

Nelson

et al. 2020

Biology of Blood and Marrow Transplantation

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“…Another report showed a GVL effect of blinatumomab in relapsed ALL patients after allo-HCT [24]. More importantly, beneficial effects of chimeric antigen receptor T cell therapy have been also reported in an ALL patient with EMR after allo-HCT [25]. The role of immune therapy has also been recently strengthened by the experience with novel immune therapies that were introduced into the treatment of advanced hematologic malignancies.…”

Section: Discussionmentioning

confidence: 98%

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Sakellari

Gavriilaki

Batsis

et al. 2019

Biology of Blood and Marrow Transplantation

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Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk. We studied 554 allo-HCT recipients for 1.8 years (range, .04 to 27.75). Ten-year CI of 10.5% for iEMR was associated only with advanced disease phase at transplantation, whereas 10-year CI of 34.8% for BMR was independently associated with pretransplant disease phase, lines of treatment, and fungal infections. Most iEMR and BMR patients (75% and 81%, respectively) received systemic treatment combined with local radiation for iEMR (26%) and donor lymphocyte infusions (16% and 28%, respectively) when feasible. Extensive chronic graft-versus-host disease (GVHD) was recorded in 47% of iEMR and 48% of BMR patients. Outcomes were poor both in iEMR (10year overall survival [OS], 18.3%) and BMR (10-year OS, 19.1%). Independent predictors of OS were disease phase, type of donor, acute and chronic GVHD, fungal infections, iEMR, and BMR. In a large population with long-term follow-up, incidence of iEMR was relatively high, developed at the late post-transplant period, and was associated only with disease phase at transplantation. Furthermore, iEMR and BMR conferred similarly poor outcomes despite systemic treatment or extensive chronic GVHD.

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“…Wang and colleagues reported that extramedullary ALL relapse in the cervix manifesting as a solid mass after allo-HSCT could be completely removed by CAR T-cell therapy [14], thus suggesting that CAR-T cells possess a highly penetrating and eradicating ability when encountering extramedullary leukemia mass. Due to a large number of capillaries, CAR-T cells should be able to infiltrate the skin and reach leukemia cells acting as subcutaneous nodules facilitated by the capillary transportation and working more efficiently, which was supported by the present case where skin nodules were significantly diminished (Fig.1a, c, d).…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report

et al. 2020

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Background: Extramedullary relapse is an important cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). This type of relapse is commonly observed in the central nervous system, while it is rare in the testicles and skin. Chimeric antigen receptor-modified T cell (CAR-T) therapy targeting CD19 has shown to be a beneficial treatment approach for relapsed/refractory B cell acute lymphoblasticleukemia (r/r BALL). Yet, few studies have reported data regarding the treatment of extramedullary BALL relapse, especially both in skin and testicle, with CART therapy. Case presentation: Here we reported a single case of a patient with relapsed BALL in skin and testicle who was successfully treated by the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy. A 29-year-old man with relapsed BALL in skin and testicle was enrolled in clinal trial involving the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy (ClinicalTrials.gov number, NCT03919240). The patient had toxicity consistent with the grade 1 cytokine release syndrome. Conclusions: ssCART-19 therapy may be used to effectively eliminate infiltrating leukemia cells in the skin and testicle with mild toxicity, which could be a much safer approach to bridge allo-HSCT, thus further improving the patient's outcome.

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Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

Cited by 14 publications

References 21 publications

Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia

Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report

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