Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1188-1194 ◽  
Author(s):  
H. J. Deeg ◽  
H. M. Shulman ◽  
J. E. Anderson ◽  
E. M. Bryant ◽  
T. A. Gooley ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Plasma Levels ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Inverse Correlation ◽  
Myelogenous Leukemia ◽  
Refractory Anemia ◽  
International Prognostic Scoring System ◽  
Free Survival ◽  
Disease Free

We carried out bone marrow transplantation (BMT) in 50 patients with myelodysplastic syndrome (MDS) who were 55.3 to 66.2 years of age (median, 58.8 years). According to the criteria of the French-American-British (FAB) classification, 13 patients had refractory anemia (RA), 19 had RA with excess blasts (RAEB), 16 had RAEB in transformation or acute myelogenous leukemia (RAEB-T/AML), and 2 had chronic myelomonocytic leukemia (CMML). According to the recently established International Prognostic Scoring System (IPSS), available for 45 patients, 2 patients were considered low risk; 14, intermediate 1 risk; 19, intermediate 2 risk; and 10, high risk. Conditioning regimens were cyclophosphamide (CY) (120 mg/kg of body weight) plus 12-Gy fractionated total-body irradiation (FTBI) (n = 15), CY plus FTBI with lung and liver shielding (n = 4), busulfan (7 mg/kg) plus FTBI (n = 4), or busulfan (16 mg/kg) plus CY (n = 27). The busulfan-plus-CY group included 16 patients in whom busulfan was targeted to plasma levels of 600 to 900 ng/mL. In these 16 patients, steady-state levels of busulfan actually achieved were 714 to 961 ng/mL (mean ± SD, 845 ± 64 ng/mL; median, 838 ng/mL). The donors were HLA-identical siblings for 34 patients, HLA-nonidentical family members for 4, identical twins for 4, and unrelated volunteers for 6. All 46 patients surviving > 21 days had engraftment, and 22 patients (44%) are surviving 9 to 80 months after BMT. Specifically, among 13 patients with RA, 1 had relapse (cumulative incidence [CI] at 3 years, 8%) and 8 are surviving, for a Kaplan-Meier (KM) estimate of survival at 3 years of 59% (disease-free survival [DSF], 53%). Among 19 patients with RAEB, 3 had relapse (CI at 3 years, 16%), and 8 are surviving disease free (KM estimate at 3 years, 46%). Among 18 patients with RAEB-T/AML or CMML, 6 had relapse (CI at 3 years, 28%), and the KM estimate of DSF at 3 years is 33%. Relapse-free survival had an inverse correlation with cytogenetic risk classification and with the risk score according to the IPSS. Survival in all FAB categories was highest among patients enrolled in a protocol in which busulfan plasma levels were targeted to 600 to 900 ng/mL. These data indicate that BMT can be carried out successfully in patients with MDS who are older than 55 years of age.

scholarly journals Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 677-681 ◽  
Author(s):  
JE Anderson ◽  
FR Appelbaum ◽  
LD Fisher ◽  
G Schoch ◽  
H Shulman ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Severe Neutropenia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Life Threatening ◽  
Total Body ◽  
Disease Free

Abstract We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease- free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

scholarly journals Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 677-681 ◽  
Author(s):  
JE Anderson ◽  
FR Appelbaum ◽  
LD Fisher ◽  
G Schoch ◽  
H Shulman ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Severe Neutropenia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Life Threatening ◽  
Total Body ◽  
Disease Free

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease- free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.

1984 ◽  
Vol 2 (5) ◽  
pp. 369-378 ◽  
Author(s):  
C B Begg ◽  
P B McGlave ◽  
J M Bennett ◽  
P A Cassileth ◽  
M M Oken
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Acute Nonlymphocytic Leukemia ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Critical Comparison ◽  
Selection Factors ◽  
Disease Free

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.

scholarly journals Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases [published erratum appears in Blood 1990 Aug 1;76(3):654]

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1728-1732 ◽  
Author(s):  
PB McGlave ◽  
P Beatty ◽  
R Ash ◽  
JM Hows
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Free Survival ◽  
Donor Bone Marrow ◽  
Grade Ii ◽  
Disease Free

Abstract From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) (“matched”). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC (“mismatche”). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft- versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte- depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1980-1987 ◽  
Author(s):  
WR Drobyski ◽  
RC Ash ◽  
JT Casper ◽  
T McAuliffe ◽  
MM Horowitz ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Entire Cohort ◽  
Graft Versus Host ◽  
Disease Free

Abstract Between January 1988 and March 1993, 48 patients received T-cell- depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T- cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high- resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease- free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

1992 ◽  
Vol 10 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G J Schiller ◽  
S D Nimer ◽  
M C Territo ◽  
W G Ho ◽  
R E Champlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
First Remission ◽  
Disease Free

PURPOSE Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.

Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation.

1991 ◽  
Vol 9 (3) ◽  
pp. 423-431 ◽  
Author(s):  
O W Press ◽  
R Livingston ◽  
J Mortimer ◽  
C Collins ◽  
F Appelbaum
Keyword(s):  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Large Cell ◽  
High Dose ◽  
Primary Therapy ◽  
Bulky Disease ◽  
Free Survival ◽  
Hodgkin's Lymphomas ◽  
Disease Free

Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.

Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy.

1989 ◽  
Vol 7 (1) ◽  
pp. 50-57 ◽  
Author(s):  
J Mortimer ◽  
M A Blinder ◽  
S Schulman ◽  
F R Appelbaum ◽  
C D Buckner ◽  
...  
Keyword(s):  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Early Death ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Late Relapse ◽  
Free Survival ◽  
High Incidence ◽  
Low Probability ◽  
Disease Free

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.

scholarly journals Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 51-58 ◽  
Author(s):  
JE Anderson ◽  
FR Appelbaum ◽  
G Schoch ◽  
T Gooley ◽  
C Anasetti ◽  
...  
Keyword(s):  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Refractory Anemia ◽  
Allogeneic Bone ◽  
Combining Data ◽  
Significant Difference ◽  
Preparative Regimen ◽  
Reasonable Approach ◽  
Disease Free

Abstract From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3-year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.

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