High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia.

1988 ◽  
Vol 6 (4) ◽  
pp. 576-582 ◽  
Author(s):  
S Riddell ◽  
F R Appelbaum ◽  
C D Buckner ◽  
P Stewart ◽  
R Clift ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Severe Toxicity ◽  
Total Body ◽  
Disease Free

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.

scholarly journals Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789]

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1015-1020 ◽  
Author(s):  
KG Blume ◽  
SJ Forman ◽  
MR O'Donnell ◽  
JH Doroshow ◽  
RA Krance ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
Total Body

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16–213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Partially Mismatched Related-Donor Bone Marrow Transplantation for Pediatric Patients With Acute Leukemia: Younger Donors and Absence of Peripheral Blasts Improve Outcome

2000 ◽  
Vol 18 (9) ◽  
pp. 1856-1866 ◽  
Author(s):  
K.T. Godder ◽  
L.J. Hazlett ◽  
S.H. Abhyankar ◽  
K.Y. Chiang ◽  
N.P. Christiansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Pediatric Patients ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Pediatric Leukemia ◽  
Total Body

PURPOSE: To extend access to bone marrow transplantation (BMT), we used partially mismatched related donors (PMRD) for pediatric patients with acute leukemia. In this report we sought to determine pretransplantation factors that might predict outcome. PATIENTS AND METHODS: Of 67 such patients, 43 had acute lymphocytic leukemia and 24 had acute myelogenous leukemia. At the time of transplantation, 41 patients were in relapse. Donors included 40 parents, 24 siblings, and three cousins. HLA disparity of two to three major antigens was detected in two thirds of the donor-recipient pairs. Conditioning therapy, including total-body irradiation and chemotherapy followed by graft-versus-host disease (GvHD) prophylaxis with partial T-cell depletion of the graft using T10B9 or OKT3, was combined with posttransplantation immunosuppression. RESULTS: Estimated probability (EP) of engraftment was 0.96 and was not affected by donor-antigen mismatch (AgMM; P = .732). EP of grades 2 to 4 acute GvHD was 0.24 and was not affected by recipient AgMM (P = .796). EP of disease-free survival was 0.26 at 3 years but improved to 0.45 when donors were younger than 30 years (P < .001). EP of relapse at 3 years was 0.41 and reduced with younger donors’ age. For patients who were in relapse at the time of transplantation, absence of blasts was associated with a lower relapse rate (0.46 v 0.84; P = .083), similar to that of patients in remission. CONCLUSION: PMRD-BMT in pediatric leukemia resulted in high engraftment and low GvHD rates. To improve outcomes, younger donors should be sought, and clinicians should attempt to reduce peripheral blasts in patients who are in relapse.

scholarly journals Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

Blood ◽  
1995 ◽  
Vol 85 (4) ◽  
pp. 1122-1131 ◽  
Author(s):  
DC Matthews ◽  
FR Appelbaum ◽  
JF Eary ◽  
DR Fisher ◽  
LD Durack ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Specific Binding ◽  
Maximum Tolerated Dose ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Refractory Anemia ◽  
Biodistribution Studies ◽  
Total Body

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.

scholarly journals Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789]

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1015-1020 ◽  
Author(s):  
KG Blume ◽  
SJ Forman ◽  
MR O'Donnell ◽  
JH Doroshow ◽  
RA Krance ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
Total Body

Abstract In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16–213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

scholarly journals Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2920-2928 ◽  
Author(s):  
DS Snyder ◽  
NJ Chao ◽  
MD Amylon ◽  
J Taguchi ◽  
GD Long ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Total Body ◽  
First Complete Remission

Abstract Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

Double-Unit Cord Blood Transplantation (DCBT) for Acute Leukemia: High Disease-Free Survival in Adults and Children with Comparable Survival in European and Minority Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3080-3080
Author(s):  
Juliet N Barker ◽  
Doris M Ponce ◽  
Anne Marie R Gonzales ◽  
Marissa N Lubin ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
European Ancestry ◽  
High Dose ◽  
Free Survival ◽  
Disease Free

Abstract Abstract 3080 As compared to single-unit CBT, DCBT may improve engraftment and protect against relapse. Therefore, we have adopted DCBT for both children and adults with acute leukemia, myelodysplasia (MDS), and myeloproliferative diseases (MPD). However, determinants of disease-free survival (DFS) have yet to be fully established. Furthermore, whether DFS after DCBT is comparable in patients of European and non-European ancestry is of special interest. Therefore, we analyzed the DFS of 75 DCBT recipients with acute leukemia in morphologic remission or aplasia (n = 69), and MDS/MPD with ≤ 5% blasts (n = 6) transplanted from 10/2005-4/2011. Nearly all patients had high-risk disease. Children 0–15 years (n = 23) had the following characteristics: median age 9 years (range 0.9–15); median weight 37 kg (range 7–72); 30% European; and 26% CMV sero-positive. Diagnoses were 43% AML (or biphenotypic), 52% ALL, and 4% MDS/MPD, and all received high-dose conditioning. The children received grafts with a median infused TNC × 107/kg of 3.3 (larger unit) and 2.6 (smaller unit), and 2% of units were 6/6 HLA-A, -B antigen, -DRB1 allele matched, 63% 5/6, and 35% 4/6. Adults ≥ 16 years (n = 52) had the following characteristics: median age 41 years (range 16–69); median weight 69 kg (range 47–105); 48% European; 69% CMV sero-positive; and diagnoses were 63% AML (or biphenotypic), 27% ALL, and 10% MDS/MPD. Fifty percent received high-dose and 50% reduced intensity conditioning. Their units had a median infused TNC/kg of 2.7 and 1.9, and 3% were 6/6 HLA-matched, 47% 5/6, and 50% 4/6. All patients (pediatric and adult) received calcineurin-inhibitor/ mycophenolate mofetil immunosuppression, and none received anti-thymocyte globulin. Sustained donor neutrophil engraftment was seen in 91% of children and 94% of adults at medians of 20 and 26 days, respectively. The incidence of grade II-IV acute GVHD by day 180 was 44% in children and 58% in adults. Day 100 transplant-related mortality (TRM) was 9% in children and 19% in adults. The 2-year relapse incidence was 9% in children and 6% in adults. With a median follow-up of survivors of 26 months (range 4–70), 2-year Kaplan-Meier estimate of DFS was 78% in children and 64% in adults (Figure). Differences in survival by age did not reach significance. Univariate analysis of variables potentially influencing 2-year DFS (with log rank estimates of significance) in all patients is shown in the Table. There were no differences in 2-year DFS according to ancestry, remission status, and conditioning intensity. There was also no difference in 2-year DFS according to engrafting unit-recipient HLA-match (4-6/6 or 10 allele), or engrafting unit infused TNC dose/kg. However, patients who were CMV seronegative had a higher 2-year DFS (85% vs 55%, p = 0.018). Multivariate analysis revealed recipient CMV serostatus was a predictor of DFS independent of patient age, and its effect was mediated by an influence on TRM. We have previously shown that DCBT extends transplant access to minority patients. We now demonstrate that DCBT can achieve high and comparable DFS in both European and non-European pediatric and adult patients with acute leukemia and MDS/MPD. While these are very encouraging results further investigation in racial/ethnic sub-groups is needed. Nonetheless, our findings support DCBT as an immediate alternative therapy for high-risk acute leukemia in patients without suitable unrelated volunteer donors, especially given the very low incidence of relapse. Disclosures: No relevant conflicts of interest to declare.

Long-Term Outcomes of Myeloablative Hematopoietic Cell Transplantation Using Total Body Irradiation Prior to Systemic Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4552-4552
Author(s):  
Cara L. Toretta ◽  
Andrzej Niemierko ◽  
Erin Coughlin ◽  
Steven L. McAfee ◽  
Bimalangshu R. Dey ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Hodgkin Lymphoma ◽  
Systemic Therapy ◽  
Total Body Irradiation ◽  
Hematopoietic Cell ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Cell Transplant ◽  
Conditioning Regimens ◽  
Total Body

Abstract Abstract 4552 Background: Myeloablative total body irradiation (TBI) may be incorporated in the condition regimen prior to hematopoietic cell transplant (HCT) for a variety of hematologic malignancies. Recent studies suggest improved patient tolerance and similar overall outcomes when TBI is administered prior to chemotherapy versus after systemic therapy. Patients and Methods: We retrospectively reviewed outcomes of adult patients (>18yrs old) who received myeloablative TBI as part of their conditioning regimen at the Massachusetts General Hospital between 1993 and 2012. All patients received TBI prior to chemotherapy; a median dose 13 Gy (range 12–16 Gy) was delivered. Patient characteristics including presenting disease, treatment course, treatment outcome and late-effects of therapy were analyzed. Results: The study cohort consisted of 116 patients; 55 patients received TBI for non-Hodgkin lymphoma (NHL), 25 for acute lymphoblastic leukemia (ALL), 16 for acute myelogenous leukemia (AML), 5 for chronic myelogenous leukemia (CML), 9 for Hodgkin lymphoma (HL), and 6 for other hematologic disease including MDS, MM, and CLL. Ten patients died of transplant-related mortality. Sixty-three patients underwent allogeneic HCT with a matched-related donor, 53 patients underwent autologous HCT, 5 patients had a tandem HCT, and the remaining patients were divided evenly among umbilical cord, haploidentical, and matched unrelated donor HCT. Twice daily TBI was administered for most patients; 56 cases received TBI three times daily. Cyclophosphamide + TBI (Cy/TBI) was the most commonly used regimen (n=100). At the time of this report, 56 patients were still alive, with a median followup of 84.7 months (range 0.5–220 months). Median survival for all 116 cases was 67 months; stratified by diagnosis: 112 months NHL, 50 months HL, 69 months ALL, 20 months AML, 17 months CML, and 36 months for other malignancies. Overall survival for the entire cohort was 53% (95% CI = 43 to 62%) and 43% (95% CI = 32 to 53%) at 5- and 10-years, respectively. Progression free or relapse-free survival (P/RFS) was 44% (95% CI = 34 to 54%) and 33% (95% CI = 23 to 43%) at 5- and 10-years, respectively. Patients with ALL had the longest P/RFS (69 months) followed by NHL (42 months). Thirteen patients developed second malignancies; 9 patients developed skin cancer, 2 were diagnosed with other solid tumors, and 2 patients had both skin cancer and another malignancy. Endocrine dysfunction such as hypothyroidism and hypogonadism was documented in 11 patients, 23 patients developed late ocular toxicity. Other late toxicities include pulmonary (14 patients), cardiac (4 patients), and 11 cases of neuropathy. None of these late toxicities were seen in patients with less than 2.5 years of survivorship after transplant. Conclusion: Similar to other reports, our results show that conditioning regimens that include the use of TBI prior to high-dose chemotherapy have OS and P/RFS that are comparable to other conditioning regimens. Appropriate screening for late toxicities of therapy should begin in the 3rd year of survivorship. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1672-1679
Author(s):  
DS Snyder ◽  
RS Negrin ◽  
MR O'Donnell ◽  
NJ Chao ◽  
MD Amylon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Total Body

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.

Outcome with the Hyper-CVAD and Imatinib Mesylate Regimen in Philadelphia (Ph) Positive Acute Lymphocytic Leukemia (ALL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1830-1830 ◽  
Author(s):  
Deborah A. Thomas ◽  
Stefan Faderl ◽  
Jorge Cortes ◽  
Susan O’Brien ◽  
Francis Giles ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Single Agent ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Molecular Response ◽  
Cell Transplant

Abstract In Ph+ ALL, complete remission (CR) rates with intensive chemotherapy such hyper-CVAD is 90%, but most patients (pts) relapse within a median time of 16 months [Kantarjian et al, JCO18:547, 2000; Kantarjian et al, Cancer101:2788, 2004]. Single agent therapy with the tyrosine kinase inhibitor imatinib mesylate in relapsed or refractory Ph+ ALL or chronic myelogenous leukemia in lymphoid blast phase yielded CR rates of 20% with rapid disease recurrence. A phase II clinical trial of concurrent hyper-CVAD and imatinib was designed to improve these results, with the initial regimen of imatinib 400 mg orally daily days 1–14 of each course (fractionated cyclophosphamide, vincristine [VCR], doxorubicin and dexamethasone alternating with high dose methotrexate and cytarabine) followed by imatinib, VCR and prednisone maintenance with intensifications months 6 and 13. Allogeneic stem cell transplant (SCT) was performed in CR if feasible. Preliminary results of first 20 pts treated were encouraging [Thomas et al, Blood103:4396, 2004]. Recent modifications included increasing dosing of imatinib to 600 mg daily days 1–14 of course 1, then daily if tolerated with courses 2–8. Maintenance was extended to 24 months with imatinib indefinitely. To date, 43 pts with Ph+ ALL have been treated from April 2004 to July 2005. Thirty-six pts had active disease, either untreated (n=31) or refractory (n=1) to one induction course without imatinib; 7 pts were in CR after one induction course without imatinib. Of 35 evaluable pts, 33 (94%) achieved CR (1 induction death, 1 failed to meet platelet criteria for CR). Median days to response was 21 days. 13 pts underwent allogeneic SCT within a median of 3 months from start of therapy (range, 1–12). After a median follow-up of 3 yrs (range 1–48 months), 1 primary refractory pt relapsed at 12 months, 1 de novo pt had isolated CNS relapse, 2 pts relapsed after allogeneic SCT (no post SCT imatinib) and 2 pts changed therapy for persistent Ph+ metaphases (1 relapsing). Deaths in CR included 5 older pts without allogeneic SCT (1 osteomyelitis, 1 mucormycosis, 1 C. difficile colitis, 1 sudden death, 1 GNR sepsis) and 4 pts after allogeneic SCT (3 graft-versus-host disease, 1 GNR sepsis). Outcome with the hyper-CVAD and imatinib regimen continues to demonstrate favorable disease-free survival rates compared with hyper-CVAD alone, particularly for the de novo group. Use of higher dose imatinib concurrently appears to be feasible. Molecular response rates appear to be improved with the higher dose imatinib; additional accrual will be required to assess impact of modifications, including role of allogeneic SCT.

Total Body Irradiation (TBI) Based Versus Chemotherapy-Based Preparative Regimens Before Autologous Stem Cell Transplant for Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5105-5105
Author(s):  
Hongwei Liu ◽  
Matthew Seftel ◽  
Allain Demers ◽  
Zoann Nugent ◽  
Garry Schroeder ◽  
...  
Keyword(s):  
Stem Cell ◽  
Total Body Irradiation ◽  
Disease Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Rank Test ◽  
High Dose ◽  
Cell Transplant ◽  
Historical Cohort ◽  
Preparative Regimen ◽  
Total Body

Abstract OBJECTIVES: The optimum high dose preparative regimen for non-Hodgkin lymphoma (NHL) patients undergoing autologous stem cell transplantation (ASCT) is unknown. We compared the radiation-based regimen of cyclophosphamide, etoposide and 12 Gy total body irradiation (CY/E/TBI) to carmustine, etoposide, cytarabine and melphalan (BEAM) in NHL patients who received ASCT. We investigated acute and long-term toxicities, disease free survival (DFS), overall survival (OS) of these two regimens. METHODS: A historical cohort study was performed at a provincial cancer centre. Cause specific survival was determined with the Kaplan-Meier method. Survival between groups was compared using the log-rank test. RESULTS: From Mar-1991 to Sep-2005, 79 patients received CY/E/TBI (n=32) or BEAM (n=47). Histology was indolent in 30 and aggressive in 49 patients. Cell source was bone marrow in six and 73 received peripheral blood progenitor cells. Prior to ASCT, ten patients were in complete remission, 47 had chemo-sensitive disease and 22 had chemo-resistant disease. There were only two cases of interstitial pneumonitis, with one in each preparative regimen group. There were six transplant related deaths; two in the BEAM group and four were in TBI group. The TBI based group has a higher mean mucosits score (p=0.03). Five year DFS was 47% and 51% in the TBI and BEAM groups, respectively (p=0.41). Five year OS was 50% and 64% for the TBI and BEAM based groups (p=0.07). Multivariate analyzes revealed that patients with more advanced disease and raised LDH at ASCT independently predicted inferior DFS. There was one case of acute myeloid leukemia and two of prostate cancer, all of whom were in the TBI group. CONCLUSIONS: In this study, a 12 Gy TBI-based regimen resulted in a similar DFS but a trend toward poorer OS and higher second malignancies than a BEAM-based regimen. However, there did not appear to be excess pulmonary acute toxicities in the TBI based group.

Sign in / Sign up

Export Citation Format

Share Document