Table 1 Summary of larger studies on Haemopoietic stem cell transplantation in Systemic lupus erythematosus
From: Haemopoietic stem cell transplantation in Systemic lupus erythematosus: a systematic review
Study (reference) | Year | Country | Study design | Patient characteristics | Interventiona,b,c | Outcome | Complications |
|---|---|---|---|---|---|---|---|
Traynor [5] | 2000 | USA | Case series | Nine patients with SLE with life or organ threatening complications not responding to several cycles of CYC (SLEDAI 17 to 37) | Autologous. MPP added to the conditioning regime | Seven patients remained in remission. No flares during follow up for > 1 year. SLEDAI score 0–5. No patient was on any immunosuppression other than a small dose of prednisolone | Two patients developed infection after stem cell harvest and one died. They did not undergo transplantation and were not included the in analysis. Two patients developed dermatomal herpes zoster and one developed pneumocystis pneumonia that resolved with treatment |
Traynor [6] | 2002 | USA | Case series | Fifteen patients with SLE with organ impairment who failed to achieve sustained remission with monthly pulsed CYC and steroids | Autologous. MPP added to the conditioning regime | SLEDAI score decreased to 5 or < 5 in 12 patients. Twelve patients were followed up for > 1 year and immunosppressants were discontinued in 10 patients. Two patients relapsed with longer follow up (> 30 months) | Neutropenic fever without culture positivity. No mortality. Two patients underwent harvesting but died before conditioning; one due to fungal infection, other due to lupus cerebritis |
Voltareli [7] | 2002 | China | Preliminary reporting | Nanjing group: ten Zhengzhou group: eighteen patients Beijing group: eight Shandong group: one (no further details) | All patients autologous. Nanjing: first three-conditioning with cytoxan and melphalan, used bone marrow. Next seven-CYC and ATG, Zhengzhou: mobilisation with CYC and ATG, bone marrow in six. No manipulation of stem cells. For conditioning total lymphoid irradiation added. Beijing group: Conditioning with CYC and TBI in four. Shandong: No details | Nanjing: eight remission, one stabilised, Zhengzhou: Complete remission in 12, partial remission in three and no remission in three. Beijing: all developed remission, Shandong: patient relapsed | Nanjing: one death due to pulmonary hypertension and cardiac failure. Beijing: Three developed CMV infections |
Jayne [8] | 2004 | Europe | Retrospective registry survey | Fifty-three patients with SLE | Autologous. In three mobilisation only with CYC or G-CSF. Source of stem cells peripheral (77%) or bone marrow (21%) or both (2%). No graft manipulation in 28. Conditioning different regimes | Out of 50 evaluable patients at 6 months 33 (66%) developed remission with SLEDAI < 3, seven (14%) developed partial remission. Ten patients developed relapse | Thirty-one severe or life threatening adverse events occurred in 28 patients including 22 infections (three deaths), five immune events, two malignancies (one death), four deaths due to progressive disease and seven deaths related to procedure |
Statkute [10] | 2005 | USA | Retrospective analysis | Twenty-eight patients with SLE with organ involvement and evidence of APLS. (Out of 46 patients who underwent HSCT) | Autologous | Twenty-one patient entered remission and nine were able to maintain remission after discontinuing all medicines. Twenty-two were on anticoagulation. After discontinuing anticoagulation in 18, 14 were free from thrombosis | No treatment related mortality. Infection during hospital stay in nine patients |
Burt [11] | 2006 | USA | Single arm trial | Fifty patients with organ or life-threatening visceral involvement due to SLE requiring minimum 20Â mg/day prednisolone or equivalent while on CYC | Autologous | Disease free survival at 5Â years 50%. Overall survival at 5Â years 84%. Four patients never entered remission. Majority showed improvement of disease activity | Two deaths prior to transplantation (One due to mucormycosis, other due to active disease). Six deaths after transplant not related to transplant (Four due to active SLE). Non-fatal infections were common during stem cell mobilisation and transplantation period |
Loh [12] | 2007 | USA | Retrospective | Out of 55 patients with SLE thirteen patients with cardiac involvement (LV dysfuction—6, pulmonary hypertension—5, mitral valve disease—3, large pericardial effusion—1) | Autologous. CD 34+ cells selected/unmanipulated stem cells. Conditioning CYC with ATG or alemtuzumab | Patients with mitral valve disease and pericardial effusion improved. All patients with LV dysfunction had at least minimal improvement. Only two patients with pulmonary hypertension had stable or improved pulmonary pressure | Three patients (two with LV dysfunction, one with pulmonary hypertension) died |
Vanikar [13] | 2007 | India | Retrospective | Twenty-seven patients with lupus nephritis | Allogenic from related donors. Unfractionated HSC transplanted into peripheral circulation, thymus and bone marrow. Non myeloablative low intensity conditioning done. | Average follow up 4.9Â years. Average disease free interval 7.35Â months | No GVHD. No life threatening side effects. Two deaths more than 2Â years later |
Gualandi [14] | 2007 | Italy | Case series | Eight patients with SLE (further information not available) | Autologous. Conditioning with CYC and thiotepa | All patients achieved complete remission. Two patients relapsed, but well controlled with treatment. Cumulative SLEDAI from 90 to 9 | No significant adverse events |
Meng [17] | 2011 | China | Controlled, non-randomized | HSCT-11, SLEDAI 20 ± 5, non-transplant—39, SLEDAI 21 ± 3 | Autologous HSCT Vs. immunesupression and assessed outcome in pregnancy after remission | HSCT-SLEDAI preconception 4 ± 1, postpartum 4 ± 1, no lupus nephritis/hypertension during pregnancy, non transplant-SLEDAI preconception 4 ± 2, postpartum 7 ± 2, 33% hypertension and 31% lupus nephritis during pregnancy | Side effects related to treatment not described |
Song [18] | 2011 | China | Controlled, non-randomised | Intervention—17 patients, Control—20 patients | Intervention-autologous HSCT, Control-conventional therapy (Steroids and CYC, three patients only steroids, four patients MMF added) | Intervention—16/17 steroids stopped within one year. SLEDAI in 5 years 32.3 ± 9.2 to 0.76 ± 0.92 (p < 0.01), Control—15/20 achieved remission, SLEDAI in 5 years 18.21 ± 5.71 to 6.28 ± 4.48 (p < 0.01) | Intervention—two patients died at 33 and 64 months due to severe pneumonia and heart failure, Control—Five patients died 2–74 months, nine had disease flares |
Pasquini [19] | 2012 | North and South America | Retrospective | SLE | Autologous—27 patients, Allogenic—3 patients | Median follow up 31 months for autologous group. No adequate data on disease outcome | Autologous—8 died (6—infection, 1—disease relapse, 1—graft failure), Allogenic—1 died due to infection |
Alchi [21] | 2012 | Europe | Retrospective | Twenty-eight patients with SLE | Autologous. Unmanipulated stem cells in 18. Conditioning regime low [10], moderate [18] intensity | Median follow up 38 months. Five year overall survival 81 ± 8%, relapse incidence 56 ± 11%, disease free survival 29 ± 9% | Thirty-one severe or life threatening adverse events. Two secondary autoimmune disorders and one lymphoproliferative disorder. Five deaths within 2 years after transplant, three due to infections, one due to secondary autoimmune disorder and one due to progressive SLE |
Leng [23] | 2017 | China | Non-controlled, non-randomized | Severe SLE—27 patients, 3 removed from analysis due to inadequate stem cell harvesting (n = 1) and being lost to follow up (n = 2) | Autologous. Conditioning CYC with ATG/ALG/TBI | 6 months—two partial remission, 21 remission, 10 years-one remained active, four lost to follow up, 16 remained in remission, 14 with lupus nephritis 4 g/24 h pre-treatment to 0 g/24 h at 5 and 10 years | Three patients died (23 days, 19 months, 3 years), 8 patients developed CMV infection |
Cao [24] | 2017 | China | Prospective non-controlled | Twenty-two patients with lupus nephritis and failed previous therapy or other significant organ involvement | Autologous | 10 patients relapsed within 10Â years of median follow up. Five year progression free survival was 67.9% | One patient died due to infection several years post-HSCT. Several patients developed opportunistic infections and 13 had CMV reactivation. Three developed secondary autoimmune disease and two had malignancies |
Clinical trials.gov [25] | 2017 | USA | Prospective non-controlled | Eight patients with severe, active lupus refractory to immunesuppression between 15 and 40Â years | Priming with rituximab, MPP and CYC. Conditioning with fludarabine, rituximab and CYC | In follow-up up to 3Â years two patients have maintained complete remission with SLEDAI 0 | Six out of eight patients died within 1Â year |