Potential beneficial and detrimental effects of JAK 1/2 inhibitors in the transplant setting
| Potentially beneficial effects . | Potentially detrimental effects . |
|---|---|
| Improvement in performance status | Withdrawal effect |
| Potential to improve the pre-HCT performance status by effective control of MF-related symptom burden36 | If stopped suddenly prior to HCT, JAK 1/2 inhibitors can cause rapid return of MF-related symptoms38,41 |
| Several transplant studies have shown a relationship between better performance status with improved survival after transplant36 | Gentle tapering over 4 to 5 days prior to HCT is recommended |
| Reduced splenomegaly | Hematopoietic recovery |
| Reduced spleen size may aid faster hematologic recovery42 | Myelosuppressive properties of JAK 1/2 inhibitors may impact hematologic recovery after HCT, limiting post-HCT use |
| Decrease in GVHD | Increased risk of infections |
| JAK 1/2 inhibitor therapy has recently been shown to be effective in reducing the risk of GVHD in a mouse model by inhibiting donor T-cell expansion and inflammatory cytokine production43,44 Beneficial effect also demonstrated on 6 patients with steroid refractory GVHD43 | Murine models show silencing of T-helper cytokine secretion and profound reduction in T-regulatory cells45 Proven increased risk of urinary tract infections and zoster infection in comparison with other available treatments46 Anecdotal case reports of opportunistic infections (reactivation of hepatitis, mycobacterial infections, and invasive fungal infections) |
| Decreased GVL effect | |
| Through impaired function of NK cells and dendritic cells | |
| Drug-drug interactions | |
| Potential for significant drug interactions with routine transplant medications such as calcineurin inhibitors and anti-fungal medications etc via CYP3A4 inhibition | |
| Tumor lysis syndrome | |
| Cases of tumor lysis syndrome reported in a recent prospective study41 | |
| It is not clear if ruxolitinib causes chemo-sensitization to drugs used in conditioning therapy |
| Potentially beneficial effects . | Potentially detrimental effects . |
|---|---|
| Improvement in performance status | Withdrawal effect |
| Potential to improve the pre-HCT performance status by effective control of MF-related symptom burden36 | If stopped suddenly prior to HCT, JAK 1/2 inhibitors can cause rapid return of MF-related symptoms38,41 |
| Several transplant studies have shown a relationship between better performance status with improved survival after transplant36 | Gentle tapering over 4 to 5 days prior to HCT is recommended |
| Reduced splenomegaly | Hematopoietic recovery |
| Reduced spleen size may aid faster hematologic recovery42 | Myelosuppressive properties of JAK 1/2 inhibitors may impact hematologic recovery after HCT, limiting post-HCT use |
| Decrease in GVHD | Increased risk of infections |
| JAK 1/2 inhibitor therapy has recently been shown to be effective in reducing the risk of GVHD in a mouse model by inhibiting donor T-cell expansion and inflammatory cytokine production43,44 Beneficial effect also demonstrated on 6 patients with steroid refractory GVHD43 | Murine models show silencing of T-helper cytokine secretion and profound reduction in T-regulatory cells45 Proven increased risk of urinary tract infections and zoster infection in comparison with other available treatments46 Anecdotal case reports of opportunistic infections (reactivation of hepatitis, mycobacterial infections, and invasive fungal infections) |
| Decreased GVL effect | |
| Through impaired function of NK cells and dendritic cells | |
| Drug-drug interactions | |
| Potential for significant drug interactions with routine transplant medications such as calcineurin inhibitors and anti-fungal medications etc via CYP3A4 inhibition | |
| Tumor lysis syndrome | |
| Cases of tumor lysis syndrome reported in a recent prospective study41 | |
| It is not clear if ruxolitinib causes chemo-sensitization to drugs used in conditioning therapy |
GVL, graft-versus-leukemia; NK, natural killer.