Scleroderma Responds to Stem Cell Transplant

SAN ANTONIO — A small group of patients with severe systemic sclerosis have shown a durable response to autologous hematopoietic stem cell transplantation, with 8 of 13 transplanted patients remaining alive after a mean follow-up of 44 months, Zora Marjanovic, M.D., reported at the annual meeting of the American College of Rheumatology.

Stem cell transplantation has in recent years been investigated for use in diseases such as scleroderma following observations that some patients with autoimmune disease who undergo transplantation for hematopoietic or other malignancies also may experience a remission of the autoimmune disease after the procedure.

In the first sequential open phase I-II study assessing the feasibility of autologous stem cell transplantation for systemic sclerosis with early visceral involvement, patients were eligible if they had rapidly progressing disease with heart, lung, or kidney involvement, Dr. Marjanovic said in a poster session.

The transplant protocol involved mobilization with cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (GCSF) or GCSF alone if the left ventricular ejection fraction (LVEF) was less than 40%.

Subsequent conditioning, which took place at least 4 weeks after mobilization, used cyclophosphamide, 200 mg/kg, or melphalan, 140 mg/m

Outcomes following reinjection of CD34+ and hematopoietic stem cells were classified as major response, partial response, no response, disease progression, or relapse. Patients were assessed every 3 months.

Of the 14 patients enrolled in the nonrandomized trial, 13 were transplanted; 1 withdrew after mobilization.

One procedure-related death occurred, she said.

Six months following transplantation, nine patients responded to treatment—six had major responses and three had partial responses.

After a mean follow-up of 44 months, 8 of the responding patients were alive, 4 have died from disease progression. One nonresponding patient remains alive.

During the follow-up period, five patients relapsed but eventually responded to reintroduction of immunosuppression by mycophenolate mofetil. Four of these were partial responses, and one was a major response, said Dr. Marjanovic of University Hospital Center Saint-Louis, Paris, France.

This trial demonstrated that autologous hematopoietic stem cell transplantation is feasible in severe scleroderma, with low toxicity and significant clinical benefits, she said.

In a report published earlier and based on 12 of the patients, toxicity associated with the procedure included infections occurring during the neutropenic period of mobilization; these were managed with antibiotics (Br. J. Haematol. 2002;119:726-39).

There were also two episodes of mucositis and three cases of mild hepatic toxicity during intensification.

Stem cell transplantation is now being compared with monthly cyclophosphamide in an ongoing phase III trial, Dr. Marjanovic said.

In the Autologous Stem Cell International Scleroderma (ASTIS) trial, patients with diffuse systemic sclerosis and visceral involvement who are at risk for severe organ dysfunction and premature mortality are being prospectively randomized to the experimental transplant procedure or standard monthly intravenous pulse therapy with cyclophosphamide.

As of October 2004, 41 patients from 16 centers in eight European countries have been enrolled. The primary end point is event-free survival during 2 years of follow-up. Information is available at www.astistrial.com

SAN ANTONIO — A small group of patients with severe systemic sclerosis have shown a durable response to autologous hematopoietic stem cell transplantation, with 8 of 13 transplanted patients remaining alive after a mean follow-up of 44 months, Zora Marjanovic, M.D., reported at the annual meeting of the American College of Rheumatology.

Stem cell transplantation has in recent years been investigated for use in diseases such as scleroderma following observations that some patients with autoimmune disease who undergo transplantation for hematopoietic or other malignancies also may experience a remission of the autoimmune disease after the procedure.

In the first sequential open phase I-II study assessing the feasibility of autologous stem cell transplantation for systemic sclerosis with early visceral involvement, patients were eligible if they had rapidly progressing disease with heart, lung, or kidney involvement, Dr. Marjanovic said in a poster session.

The transplant protocol involved mobilization with cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (GCSF) or GCSF alone if the left ventricular ejection fraction (LVEF) was less than 40%.

Subsequent conditioning, which took place at least 4 weeks after mobilization, used cyclophosphamide, 200 mg/kg, or melphalan, 140 mg/m

Outcomes following reinjection of CD34+ and hematopoietic stem cells were classified as major response, partial response, no response, disease progression, or relapse. Patients were assessed every 3 months.

Of the 14 patients enrolled in the nonrandomized trial, 13 were transplanted; 1 withdrew after mobilization.

One procedure-related death occurred, she said.

Six months following transplantation, nine patients responded to treatment—six had major responses and three had partial responses.

After a mean follow-up of 44 months, 8 of the responding patients were alive, 4 have died from disease progression. One nonresponding patient remains alive.

During the follow-up period, five patients relapsed but eventually responded to reintroduction of immunosuppression by mycophenolate mofetil. Four of these were partial responses, and one was a major response, said Dr. Marjanovic of University Hospital Center Saint-Louis, Paris, France.

This trial demonstrated that autologous hematopoietic stem cell transplantation is feasible in severe scleroderma, with low toxicity and significant clinical benefits, she said.

In a report published earlier and based on 12 of the patients, toxicity associated with the procedure included infections occurring during the neutropenic period of mobilization; these were managed with antibiotics (Br. J. Haematol. 2002;119:726-39).

There were also two episodes of mucositis and three cases of mild hepatic toxicity during intensification.

Stem cell transplantation is now being compared with monthly cyclophosphamide in an ongoing phase III trial, Dr. Marjanovic said.

In the Autologous Stem Cell International Scleroderma (ASTIS) trial, patients with diffuse systemic sclerosis and visceral involvement who are at risk for severe organ dysfunction and premature mortality are being prospectively randomized to the experimental transplant procedure or standard monthly intravenous pulse therapy with cyclophosphamide.

As of October 2004, 41 patients from 16 centers in eight European countries have been enrolled. The primary end point is event-free survival during 2 years of follow-up. Information is available at www.astistrial.com

SAN ANTONIO — A small group of patients with severe systemic sclerosis have shown a durable response to autologous hematopoietic stem cell transplantation, with 8 of 13 transplanted patients remaining alive after a mean follow-up of 44 months, Zora Marjanovic, M.D., reported at the annual meeting of the American College of Rheumatology.

Stem cell transplantation has in recent years been investigated for use in diseases such as scleroderma following observations that some patients with autoimmune disease who undergo transplantation for hematopoietic or other malignancies also may experience a remission of the autoimmune disease after the procedure.

In the first sequential open phase I-II study assessing the feasibility of autologous stem cell transplantation for systemic sclerosis with early visceral involvement, patients were eligible if they had rapidly progressing disease with heart, lung, or kidney involvement, Dr. Marjanovic said in a poster session.

The transplant protocol involved mobilization with cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (GCSF) or GCSF alone if the left ventricular ejection fraction (LVEF) was less than 40%.

Subsequent conditioning, which took place at least 4 weeks after mobilization, used cyclophosphamide, 200 mg/kg, or melphalan, 140 mg/m

Outcomes following reinjection of CD34+ and hematopoietic stem cells were classified as major response, partial response, no response, disease progression, or relapse. Patients were assessed every 3 months.

Of the 14 patients enrolled in the nonrandomized trial, 13 were transplanted; 1 withdrew after mobilization.

One procedure-related death occurred, she said.

Six months following transplantation, nine patients responded to treatment—six had major responses and three had partial responses.

After a mean follow-up of 44 months, 8 of the responding patients were alive, 4 have died from disease progression. One nonresponding patient remains alive.

During the follow-up period, five patients relapsed but eventually responded to reintroduction of immunosuppression by mycophenolate mofetil. Four of these were partial responses, and one was a major response, said Dr. Marjanovic of University Hospital Center Saint-Louis, Paris, France.

This trial demonstrated that autologous hematopoietic stem cell transplantation is feasible in severe scleroderma, with low toxicity and significant clinical benefits, she said.

In a report published earlier and based on 12 of the patients, toxicity associated with the procedure included infections occurring during the neutropenic period of mobilization; these were managed with antibiotics (Br. J. Haematol. 2002;119:726-39).

There were also two episodes of mucositis and three cases of mild hepatic toxicity during intensification.

Stem cell transplantation is now being compared with monthly cyclophosphamide in an ongoing phase III trial, Dr. Marjanovic said.

In the Autologous Stem Cell International Scleroderma (ASTIS) trial, patients with diffuse systemic sclerosis and visceral involvement who are at risk for severe organ dysfunction and premature mortality are being prospectively randomized to the experimental transplant procedure or standard monthly intravenous pulse therapy with cyclophosphamide.

As of October 2004, 41 patients from 16 centers in eight European countries have been enrolled. The primary end point is event-free survival during 2 years of follow-up. Information is available at www.astistrial.com