#506 Improved disease-free survival in children with high-risk all following autologous bone marrow transplantation (ABMT) that utilizes chemopurging post ABMT modulation of multidirug resistance (MDR) and immunochemotherapy

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4- hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.

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Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia

Blood ◽

10.1182/blood.v74.1.501.501 ◽

1989 ◽

Vol 74 (1) ◽

pp. 501-506 ◽

Cited By ~ 68

Author(s):

SD Rowley ◽

RJ Jones ◽

S Piantadosi ◽

HG Braine ◽

OM Colvin ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Ex Vivo ◽

Autologous Bone Marrow Transplantation ◽

Disease Free Survival ◽

Autologous Bone Marrow ◽

Free Survival ◽

Autologous Bone ◽

Acute Nonlymphoblastic Leukemia

Abstract We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4- hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.

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Autologous bone marrow transplantation for patients with poor-prognosis lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.8.1303 ◽

1988 ◽

Vol 6 (8) ◽

pp. 1303-1313 ◽

Cited By ~ 119

Author(s):

S C Gulati ◽

B Shank ◽

P Black ◽

J Yopp ◽

B Koziner ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Combination Chemotherapy ◽

Poor Prognosis ◽

Autologous Bone Marrow Transplantation ◽

Disease Free Survival ◽

Autologous Bone Marrow ◽

Free Survival ◽

Autologous Bone ◽

Disease Free

Review of prognostic factors at Memorial Hospital in New York City has shown that adult patients with large-cell lymphoma (diffuse histiocytic lymphoma by Rappaport classification) who have high lactic dehydrogenase (LDH) and/or bulky mediastinal or abdominal disease are destined to do poorly with conventional combination chemotherapy, with a 2-year disease-free survival of about 20%. Patients who relapse after conventional combination chemotherapy have a similar poor prognosis. Thirty-one such patients with lymphoma were studied to evaluate the efficacy of intensive radiotherapy (hyperfractionated total body irradiation [TBI] [1,320 rad]), and cyclophosphamide (60 mg/kg/d for two days) followed by autologous bone marrow transplantation (ABMT). Our results show a disease-free survival advantage (P = .002) for 14 patients who underwent ABMT immediately after induction of remission with 79% surviving at a median follow-up 49.2+ months, compared with a median survival of 5.2 months for 17 patients administered ABMT while in relapse and/or after failing conventional treatment. Our results support the use of aggressive therapy as early treatment for patients with poor prognostic features.

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Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

Blood ◽

10.1182/blood.v81.2.311.311 ◽

1993 ◽

Vol 81 (2) ◽

pp. 311-318 ◽

Cited By ~ 48

Author(s):

CA Linker ◽

CA Ries ◽

LE Damon ◽

HS Rugo ◽

JL Wolf

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Relapse Rate ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Disease Free Survival ◽

Autologous Bone Marrow ◽

First Remission ◽

Autologous Bone

Abstract We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.

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Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.6.962 ◽

1991 ◽

Vol 9 (6) ◽

pp. 962-969 ◽

Cited By ~ 40

Author(s):

G Dini ◽

E Lanino ◽

A Garaventa ◽

D Rogers ◽

S Dallorso ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Partial Remission ◽

Autologous Bone Marrow Transplantation ◽

Progression Free Survival ◽

Autologous Bone Marrow ◽

High Dose ◽

Free Survival ◽

Autologous Bone

From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR.

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Treatment of High-Risk Solid Tumors of Childhood with Intensive Therapy and Autologous Bone Marrow Transplantation

Pediatric Clinics of North America ◽

10.1016/s0031-3955(16)38084-1 ◽

1991 ◽

Vol 38 (2) ◽

pp. 393-424 ◽

Cited By ~ 37

Author(s):

Robert C. Seeger ◽

C. Patrick Reynolds

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

High Risk ◽

Solid Tumors ◽

Marrow Transplantation ◽

Intensive Therapy ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

Autologous Bone

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Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

Blood ◽

10.1182/blood.v81.2.311.bloodjournal812311 ◽

1993 ◽

Vol 81 (2) ◽

pp. 311-318 ◽

Cited By ~ 1

Author(s):

CA Linker ◽

CA Ries ◽

LE Damon ◽

HS Rugo ◽

JL Wolf

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Relapse Rate ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Disease Free Survival ◽

Autologous Bone Marrow ◽

First Remission ◽

Autologous Bone

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.

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