41 patients were treated between Aug 2012 and Jan 2022. The baseline characteristics of the patients treated are shown in Table 1. 34 patients had MF and 7 had SS. The cohort was heavily pretreated with a median of 4 prior systemic therapies. Large cell transformation in the skin and or nodes was present in 59% of MF and 14% of SS patients. 6 patients with MF had stage IVB disease with visceral involvement including muscle, brain, bone, breast and lung. The single patient with brain involvement had a CR to low dose whole brain radiotherapy and temozolomide prior to transplant. Global response rates to prior therapy and post TSEB pre-transplant are shown in Table 2. Specifically 24 (59%) patients were in CR, 16 (39%) in PR and 1(2%) patient had SD post TSEBT pre-transplant. 2 patients had progressive disease in the skin only following prior systemic therapy and responded to TSEBT with one in CR and one in PR post TSEBT pre-transplant. 8 patients had TSEBT omitted because either they had extensive TSEBT in the past and were close to skin tolerance, or because previous TSEBT had been ineffective. Of the 8 patients who had TSEBT omitted 3 were in CR, 4 in PR and 1 had SD at the pre-Day 0 time point. Of the 33 patients who received TSEBT, 9 received low dose 12 Gy/8 f/2 weeks, 19 received 24 Gy/16 f/4 weeks and 5 received 30 Gy/20 f/5 weeks. All patients received TLI and ATG as per protocol.

27 MF/SS patients had a matched unrelated donor (MUD), 11 a sibling (SIB) matched donor and 3 a Haplotype donor. (See Table 1.)

The median donor CD34+cell dose was 6.41 × 106/Kg (range 2.44–9.98), and the median donor CD3+ cell dose was 21.3 × 107/Kg (range 7.9–98.9). Between Day +60 and Day +100, 23 of 37 (62%) evaluable patients had full donor chimerism. 4 patients had graft rejection/failure, 2 of whom had a second transplant and 2 died of progressive disease. Of the 2 who had a second transplant, 1 is alive in CR and one is alive with SD.

Two patients subsequently lost their graft and recovered autologous haematopoiesis, while 3 others converted to full donor chimerism, in 2 cases following donor lymphocyte therapy (DLI). Ten patients remained mixed chimeras.

10 patients received DLI at a median of 113 days post-transplant (range 27 to 432 days). 4 patient received a second DLI. The reasons for DLI were relapse in 6 patients, relapse and low chimerism in 1 patient and low chimerism in 3 patients. 4 patients went into CR following DLI. Of these 4 patients 3 remain alive in CR and 1 remains alive with disease on treatment.

All patients received their hematopoietic cell infusions as an inpatient. The median length of inpatient stay was 36 days (range 24–152 days). Post transplant toxicity and complications are shown in Table 3.

18 (44%) patients developed Acute GVHD. The sites involved were skin (n = 11), eyes (n = 1), liver (n = 3), lungs (n = 2), gastrointestinal (n = 7) and oral (n = 1), with 4 patients having more than one site involved. Acute GVHD was Grade 2 or higher in 13 (31.7%) patients (G1 = 5, G2 = 6, G3 = 2, G4 = 5). The cumulative incidence of GVHD is shown in Fig. 1. 4 patients died related to complications of acute GVHD. 2 had SS and died of acute skin GVHD at 3.1 and 2.6 months post-transplant. 2 had MF and died of acute skin GVHD at 7.5 months and acute lung GVHD at 4.7 months.

Cumulative incidence of acute GVHD.

16 (39%) patients developed chronic GVHD. The sites involved were skin (n = 11), eyes (n = 5), oral (n = 2), GI (n = 4), lung (n = 2) with 8 patients having more than 1 site involved. Chronic GVHD was Grade 2 or higher in 10 (24%) patients (G1 = 6, G2 = 6, G3 = 1, G4 = 3). 3 patients died of complications related to late GVHD. All three patients had MF and died in CR. One patient died at 16.4 months of chronic GVHD complications affecting GI, skin and liver. One patient died at 31.4 months of lung and liver chronic GVHD complications. One patient died at 42.6 months of skin, GI and lung chronic GVHD complications.

2 patients developed Grade 2 skin GVHD, 2.5 months and 18 months following DLI.

The median follow up post-transplant of all patients was 5.27 years (range 0.16 to 9.68 years). At D + 90 post-transplant 27 (66%) patients were in CR, 7 (17%) in PR, 1 (2%) had SD and 6 (15%) had PD. Of the 6 patients who had PD, 2 died before D + 90. Of these 2 patients one had stage IVB MF and progressed with liver metastases and the other had SS (stage IVA2) and progressed in the blood. Both died of sepsis complications. Of 34 patients with MF at D + 90 23 (67%) were in CR, 5 (15%) in PR, 1 (3%) had SD and 5 (15%) had PD. 7 patients had SS and at D + 90 4 (57%) were in CR, 2 (29%) in PR and 1 (14%) had PD.

The OS, PFS and EFS results are shown in Fig. 2. Median OS was 4.09 years with 2-year OS of 61.5% and 5-year OS of 37.7%. Median PFS was 2.62 years with 2-year PFS of 52.5% and 5-year PFS of 37.1%. Median EFS was 1.29 years with 2-year EFS of 45% and 5 year EFS of 36.1%.

Kaplan–Meier estimates of OS (black line), PFS (red line). EFS (green line).

The median OS in MF patients was 4.09 years and not reached in the SS patients. The 5-year OS in MF was 36.7% and SS 57.1% (p = 0.70 NS). The median survival in patients <60 y was 3.55 years compared to 4.88 years >60 y (p = 0.98 NS) There was no significant difference in survival by Stage. The median OS in patients with large cell transformation (LCT) was 2.83 years compared to 5.3 years in patients with no LCT but this was not significant (p = 0.17). The median OS by transplant type was 4.84 years for MUD, 3.55 years for SIB and 0.66 years for Haplotype-matched. Comparing the OS of the MUD/SIB patients versus the Haplotype-matched patients was significant but should be interpreted with caution given the small number of Haplotype-matched transplants (n = 3) (p = 0.03). Importantly, the median OS in patients in CR at transplant D0 was 4.88 years compared to 1.53 years if not in CR, but did not reach significance (p = 0.054). The median PFS in patients in CR at transplant D0 was 4.88 years compared to 0.62 years if not in CR which did reach significant (p = 0.02) We found no other significant findings on univariate analysis, full details are available in the Supplementary Table.

The cumulative incidence of PD/R post-transplant is shown in Fig. 3. The 5-year cumulative incidence was 52.7%. The cumulative incidence of PD/R in those with CR to prior therapy was 37.5% compared to 51.9% in those not in CR (Grays test p = 0.67 NS). The cumulative incidence of PD/R in those with CR post TSEB at D0 was 20.8% compared to 70.6% in those not in CR which was significantly different (Grays test p = 0.006) (See Fig. 3).

Cumulative incidence of progressive disease/relapse in all, CR at D0 and NCR at D0 patients.

18 patients developed disease progression or relapse post-transplant (PD/R). 9 patients progressed in the skin, 1 in the blood, 4 had nodal progression and 4 had visceral progression. At last follow up 3 of these patients are alive, 2 in CR and 1 with active disease on chemotherapy. Of the CR patients, one went into CR following DLI and remains in CR at last follow-up 8.12 years post-transplant. The other patient had no donor for DLI and was treated with Brentuximab with further PD and then liposomal doxorubicin achieving a CR. This patient subsequently had a second transplant with Flu/Mel/Alemtuzumab conditioning and remains in CR at last follow-up 2.53 years post-first transplant.

At last follow-up 17 patients are alive in CR, 2 patients are alive with disease and 22 patients have died. Of the 22 deaths, 13 were due to disease progression and 9 deaths were due to non-relapse/progression. These consisted of 4 patients who died due to acute GVHD at 2.6 months, 3.1 months, 4.7 months and 7.5 months post-transplant with 3 patients in CR and one patient in PR at the time of death. 3 patients died due to chronic GVHD at 16.4 months, 31.4 months and 42.6 months post-transplant with all 3 patients in CR at the time of death. 1 patient died of pneumonia during the COVID pandemic at 5.3 years post-transplant in CR with chronic ocular GVHD. 1 patient died of metastatic colorectal cancer at 4.88 years post-transplant in CR. The cumulative incidence of NRM is shown in Fig. 4. The 1-year NRM was 9.8%, 2year NRM 12.6% and 5-year NRM 23.4%.

Cumulative incidence of Nn-Relapse Mortality.