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Allogeneic Stem-Cell Transplantation From Related and Unrelated Donors in Older Patients With Myeloid Leukemia

From the Department of Hematology and Oncology, Albert Ludwigs University Medical Center, Freiburg, Germany.

Address reprint requests to J. Finke, MD, Albert Ludwigs University Medical Center, Department of Hematology/Oncology, Hugstetter Str 55, D-79106 Freiburg, Germany; email: finke{at}mm11.ukl.uni-freiburg.de.

	ABSTRACT

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Purpose: To improve outcome for older patients with poor-prognosis myeloid malignancies by using allogeneic hematopoietic stem-cell transplantation (alloHSCT) from unrelated and sibling donors after reduced-intensity conditioning (RIC).

Patients and Methods: Nineteen older patients (median age, 64 years; range, 60 to 70 years) with active myeloid malignancies were treated with an RIC regimen that was based on fludarabine, melphalan, and carmustine followed by alloHSCT from matched unrelated (n = 12) or sibling donors (n = 7). Before transplantation, patients had a median of 50% bone marrow blasts (range, 0% to 70%). Graft-versus-host-disease (GvHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil or methotrexate. Eleven of 12 patients with an unrelated donor also received anti–T-lymphocyte globulin (ATG).

Results: Engraftment was successful for all 19 patients. Seventeen assessable patients achieved complete response (CR). Four patients experienced relapse; three achieved CR again after donor lymphocyte infusion (n = 1) or a second alloHSCT (n = 2). Six patients died as a result of relapse (n = 2), GvHD-associated complications (n = 2), or fungal infections (n = 2), resulting in a 1-year nonrelapse mortality rate of 22%. With a median follow-up of 825 days (range, 595 to 1,028 days), 13 of 19 patients are alive, resulting in a 1-year survival rate of 68% (95% confidence interval, 48% to 89%).

Conclusion: In older patients with untreated poor-prognosis leukemia, this RIC regimen combined with alloHSCT sufficiently reduces the leukemic burden, resulting in a high CR rate. When ATG is added, matched unrelated donor transplantation can be performed safely in older patients. For these patients, early transplantation after diagnosis offers a fair chance of cure.

	INTRODUCTION

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THE PROGNOSIS FOR older patients (age 60 years) with acute myeloid leukemia (AML) is poor, and cure is rarely achieved using standard conventional chemotherapy alone. Allogeneic hematopoietic stem-cell transplantation (alloHSCT) has the highest potential of curing patients, but the use of high-dose myeloablative conditioning regimens is limited to younger patients (< 50 to 55 years) who are in good clinical condition. Advanced age and comorbidities predispose patients to an increased risk of treatment-related morbidity and mortality.¹ Apart from the eradication of malignant cells by conditioning regimens, the main therapeutic benefit of alloHSCT is ascribed to the immune-mediated graft-versus-leukemia effect.² Sibling donor transplantation for patients with AML or myelodysplastic syndrome (MDS) who are older than 60 years has shown sustained remissions after reduced-intensity conditioning (RIC) regimens,^3,4 as well as after conventional conditioning.⁵ However, older patients often lack a healthy HLA-identical relative, and only limited data are available regarding matched unrelated donor (MUD) transplantation for patients in this extended age group.⁶

We conducted a phase II study of 19 older patients aged 60 to 70 years with active, poor-prognosis myeloid malignancies. Seventeen of 19 patients achieved complete response (CR) after an RIC regimen containing fludarabine, carmustine, and melphalan followed by transplantation with stem cells from MUDs (n = 12) or sibling donors (n = 7). Thirteen patients are alive in CR at a median follow-up of 825 days (range, 595 to 1,028 days).

	PATIENTS AND METHODS

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Patient Characteristics
Patient characteristics are listed in Table 1. Diagnoses were AML (n = 2), MDS (n = 3), osteomyelofibrosis (n = 1), and secondary AML (n = 13); 11 were diagnosed after MDS and two were diagnosed after radiotherapy and chemotherapy for Hodgkin’s disease. Median duration of disease until transplantation was 345 days (range, 49 to 1,250 days). Six patients were untreated, whereas five patients had untreated relapse before conditioning. Five patients had experienced treatment failure with earlier rounds of standard chemotherapy. The median percentage of blasts in the marrow was 50% (range, 0% to 90%) and six patients had cytogenetic abnormalities (Table 1). No patient had undergone a previous transplantation. Pretransplantation cytomegalovirus (CMV) serology was positive in 11 patients; three male transplant recipients had a female donor. Two patients had known fungal infection before transplantation.

Conditioning Regimen and Graft-Versus-Host-Disease (GvHD) Prophylaxis
The conditioning regimen for all 19 consecutive patients older than 60 years consisted of a fludarabine-based RIC regimen (fludarabine 150 mg/m², carmustine 300 mg/m², and melphalan 110 mg/m²) as previously described.⁹ Patients received this conditioning therapy within an open-label phase II trial with an amendment for MUD approved by the local institutional review board and ethics committee after patients provided informed written consent. The trial was carried out according to the Helsinki Declaration.

GvHD prophylaxis consisted of intravenous cyclosporine starting at day -3 at a dose of 2.5 mg/kg bid (trough level, 250 to 350 ng/mL) in combination with mycophenolate mofetil 1,000 mg twice daily intravenously starting at day -1 in 18 patients or mini-methotrexate (5 mg/m² on days +1, +3, and +6) in the first patient. Cyclosporine and mycophenolate mofetil were given orally as soon as the patient was able to swallow. In addition, patients with an MUD received anti–T-lymphocyte globulin (ATG) 40 to 60 mg/kg body weight (ATG-S; Fresenius, Graefelfing, Germany; n = 11),⁷ except for patient 514, who had transfusion-refractory thrombocytopenia resulting from platelet autoantibodies before transplantation. Standard supportive care and, in the case of CMV reactivation, preemptive ganciclovir or foscarnet therapy, was given as described previously.⁷ All patients received recombinant human granulocyte colony-stimulating factor (filgrastim; Amgen, Munich, Germany) starting at day +7.

Evaluation and Statistics
Acute and chronic GvHD was assessed using the criteria of Przepiorka et al¹⁰ and Shulman et al,¹¹ and organ regimen-related toxicity was graded according to the World Health Organization criteria.¹²

Day of engraftment was defined as the first of 3 consecutive days with leukocytes 1 x 10⁹/L. CR was defined as complete donor chimerism (CC) with an absence of cytogenetic abnormalities and blasts in the bone marrow biopsy examination. For sex-different transplantation, interphase fluorescent in situ hybridization (FISH) examination for XX/XY chromosomes was performed (CEP X/Y DNA probe kit; Vysis, Stuttgart, Germany); in sex-matched transplantation, chimerism analysis was performed by variable number of tandem repeats polymerase chain reaction after screening for an informative marker.⁹

The Kaplan-Meier method was used to calculate disease-free survival, overall survival (OS), and the probability of nonrelapse mortality (TRM) using GraphPad-Prism software (Graph Pad Software Inc, San Diego, CA).

	RESULTS

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Engraftment
No primary or secondary graft failure occurred. All 19 patients achieved a leukocyte level 1 x 10⁹/L at a median of day +11 (range, 8 to 24 days). Stable platelet counts 20 x 10⁹/L and 50 x 10⁹/L were reached in 16 patients at a median of day +15 (range, 8 to 42 days) and day +21 (range, 11 to 104 days), respectively. Three patients died before stable platelet engraftment.

Chimerism
FISH analysis, performed on bone marrow biopsies from five patients, showed CC in all patients at day +30 and in three of five patients at day +100. Variable number of tandem repeats polymerase chain reaction showed CC surviving until day +30 in all patients (n = 17) and until day +100 in 15 of 17 patients.

Treatment-Related Toxicities
Clinically relevant acute GvHD (aGvHD) grade 2 or higher developed in 10 (59%) of 17 patients, and grade 3/4 aGvHD developed in five (29%) of 17 assessable patients surviving until day +30. After MUD transplantation, aGvHD grade 2 or higher developed in five (46%) of 11 and grade 3/4 developed in two (18%) of 11 patients. After sibling donor transplantation, aGvHD grade 2 or higher was observed in five (83%) of six patients, and grade 3/4 was observed in three (50%) of six assessable patients. No significant difference between MUD and sibling donor transplantation was observed. Limited chronic GvHD (cGvHD) was experienced by four of 17 patients, and extensive cGvHD was experienced by seven of 17 patients. After MUD transplantation, four of 11 patients developed limited cGvHD. Extensive cGvHD was observed in two of 11 MUD transplantations and in five of six sibling transplantations. Five of these seven patients with extensive cGvHD are still receiving immunosuppressive therapy, and only one of five patients received more than 7.5 mg/d of prednisolone. All other patients are no longer receiving immunosuppressive therapy.

Organ Toxicity
All patients had WHO grade 4 hematologic toxicity; none had fever greater than grade 2. Grade 3/4 mucositis occurred in one patient, and grade 3/4 lung toxicity with pneumonia was seen in nine patients (47%), with one requiring ventilation therapy. Renal function was temporarily impaired, with grade 3/4 toxicity seen in five patients, necessitating short-term dialysis. No patient had to continue dialysis. In addition, grade 3/4 liver toxicity, cardiotoxicity, and neurotoxicity are listed in Table 1.

Outcome
Six patients died. Two patients died as a result of early fungal infection and two patients died as a result of infections and multiorgan failure in the context of GvHD. Two patients died as a result of relapse. The overall 1-year TRM rate was 22%. No Epstein-Barr virus–associated lymphoproliferative disease was observed, and no patient died from CMV infection. All 17 patients surviving day +30 achieved CR by standard diagnostic procedures and chimerism analysis. Patient 511, who died on day +28, showed no persistence of MDS in the bone marrow examination at autopsy. In patient 459, no autopsy was performed. Four patients experienced relapse, with pretransplantation bone marrow blast infiltrations of 4%, 17%, 60%, and 70%. One patient died from relapsing AML despite cessation of immunosuppressive therapy and subsequent donor lymphocyte infusions (DLI), and one patient died with blast crisis in osteomyelofibrosis and achieved only a short-term CR after a second alloHSCT. The other two patients are alive: one patient achieved secondary CR after second alloHSCT and the other achieved secondary CR after cessation of immunosuppression and DLI. The last patient experienced relapsed again on day +643 with an intracerebral chloroma without systemic hematologic relapse. He received cranial irradiation therapy and achieved remission.

As of October 1, 2002, 13 of 19 patients were alive, with a median follow-up of 825 days (range, 595 to 1,028 days), and all patients are in hematologic CR. The 1-year OS rate is 68%, and the disease-free survival rate is 61% (95% confidence interval, 40% to 84%; Fig 1).

View larger version (21K): [in this window] [in a new window]   Fig 1. Probability of overall survival (OS), disease-free survival (DFS), and nonrelapse mortality (TRM; %) in 19 patients who received transplants from matched sibling (n = 7) or unrelated donor (n = 12), with a median follow-up of 825 days (range, 595 to 1,028 days).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

The extensive immunosuppressive and myeloablative potential of the fludarabine, carmustine, and melphalan protocol is documented by our results with engraftment in 19 (100%) of 19 patients. This compares favorably with a recently published 20% rate of graft failure in older patients after less intense immunosuppressive conditioning.⁴

In addition, the achievement of CR in all patients who were assessable at day +30 (17 [89%] of 19 patients) demonstrates the feasibility, efficacy, and intensity of our protocol to eradicate leukemia compared with the 44% (19 of 45) of all patients who underwent transplantation observed in the above-mentioned study.⁴ A limited amount of data has been available to date for transplants from unrelated donors for patients in this extended age group. Our results, with an OS rate of 68% (95% confidence interval, 48% to 89%) and no difference between MUD and sibling transplantation, compare well with OS rates of 50% to 72% in surveys of older patients that included a maximum of only eight patients after MUD transplantation^6,14,15 or HLA-matched sibling transplantation and T-cell depletion.¹⁶ Of note, in a recent publication,¹ all 14 patients older than 50 years died after conventional conditioning for unrelated donor transplantation using anti-CD6 antibodies for T-cell depletion as GvHD prophylaxis. With our protocol, the incidence of severe acute GvHD was relatively low after MUD transplantation. This may be due to the additional application of ATG in this patient group.⁷ No patient died from aGvHD.

High leukemic burden at alloHSCT has proven to be the most important risk factor for a poor outcome.^17,18 This was especially true for patients with high-risk leukemia and 30% leukemic blasts in the marrow before transplantation, who had a cumulative incidence of relapse at 1 year of 71% after unrelated donor transplantation.¹⁸ Of note, all of our primary untreated patients (n = 6) and 80% of patients with an untreated relapse (n = 5) with in part more than 50% blasts in the marrow showed a CR with 100% CC at day +30 examination, confirming the myeloablative efficacy of our protocol. All hematologic relapses (n = 4) occurred at a median of day +107 (range, 83 to 176 days). Our experience in younger patients with similar leukemia risk indicates that relapse later than 1.5 years is rather unlikely. Despite the aggressiveness of the leukemia before transplantation, three of four patients who experienced relapse were able to achieve sustained hematologic CR again after DLI (n = 1) and after second transplantation (n = 2). Importantly, both patients with treatment-related AML, being at high risk for relapse and TRM after alloHSCT,¹⁹ are in sustained CR at day +651 and +825. Two patients died before engraftment as a result of fungal infections despite early therapy with amphotericin B after previous prolonged cytopenias, confirming the necessity of new antifungal strategies.²⁰ To avoid this complication, early alloHSCT during the disease course would be an option. TRM at day +100 (10%) is identical to recently published results after autologous hematopoietic stem-cell transplantation in the same age group.²¹ The 1-year TRM rate of 22% compares favorably with the literature^1,5,14 and recently published results of the European Bone Marrow Transplantation Group in patients with secondary AML/MDS, with a TRM rate of 73% after alloHSCT in patients older than 40 years.²² Given the generally poor outcomes, the authors of this study suggest avoiding alloHSCT with an unrelated donor in patients older than 40 years.

Although our recipient cohort is small and the observation time (median, 825 days) is limited, we conclude that RIC and instituting adequate supportive measures followed by alloHSCT is feasible and can be carried out successfully in patients older than 60 years with poor-prognosis myeloid malignancies. Our results of a similar outcome of MUD transplantation compared with sibling transplantation may be due to the addition of ATG for GvHD prevention.⁷ Therefore, in patients lacking a healthy sibling donor, which is likely to be a problem in this advanced-age group, a search for an unrelated donor should be rapidly initiated. By combining fludarabine with moderate doses of stem-cell toxic alkylating agents, our regimen sufficiently reduced the leukemic burden, resulting in a high CR rate. Thus patients with untreated leukemia and MDS have a chance of achieving sustained CR. If older patients are offered early transplantation after diagnosis of myeloid malignancies in the same way as is done for younger patients, complications might be reduced.

	ACKNOWLEDGMENTS

 
We thank E. Lenartz for donor search and coordination; I. Matt for data management; R. Kunzmann for FISH analysis; U. Tritschler and S. Zehbe for technical assistance in the laboratory; M. Follo for language assistance; H. Arnold, F. Hirsch, Th. Fischer, and J. Mezger for patient referral; the nurses and fellows of ward Löhr for their excellent patient care; and R. Mertelsmann for continuous support.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. Soiffer RJ, Weller E, Alyea EP, et al: CD6+ donor marrow T-cell depletion as the sole form of graft-versus-host disease prophylaxis in patients undergoing allogeneic bone marrow transplant from unrelated donors. Blood 19:1152–1159, 2001

2. Slavin S, Nagler A, Naparstek E, et al: Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91:756–763, 1998[Abstract/Free Full Text]

3. Giralt S, Estey E, Albitar M, et al: Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy. Blood 89:4531–4536, 1997[Abstract/Free Full Text]

4. McSweeney PA, Niederwieser D, Shizuru JA, et al: Hematopoietic cell transplantation in older patients with hematologic malignancies: Replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97:3390–3400, 2001[Abstract/Free Full Text]

5. Deeg HJ, Shulman HM, Anderson JE, et al: Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood 95:1188–1194, 2000[Abstract/Free Full Text]

6. Nagler A, Or R, Napastek E, et al: Matched unrelated bone marrow transplantation (BMT) using a non-myeloablative conditioning regimen. Blood 92:S289a, 1998 (abstr, suppl)

7. Finke J, Bertz H, Schmoor C, et al: Allogeneic bone marrow transplantation from unrelated donors using in vivo anti-T-cell globulin. Br J Haematol 111:303–313, 2000[CrossRef][Medline]

8. Engelhardt M, Bertz H, Afting M, et al: High- versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34+ immunoselection. J Clin Oncol 17:2160–2172, 1999[Abstract/Free Full Text]

9. Wäsch R, Reisser S, Hahn J, et al: Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation. Bone Marrow Transplant 26:243–250, 2000[CrossRef][Medline]

10. Przepiorka D, Weisdorf D, Martin P, et al: Consensus conference on acute GvHD grading. Bone Marrow Transplant 15:825–828, 1995[Medline]

11. Shulman HM, Sullivan KM, Weiden PL, et al: Chronic graft-versus-host syndrome in man: A long term clinicopathologic study of 20 Seattle patients. Am J Med 69:204–217, 1980[CrossRef][Medline]

12. Miller AB, Hoogstraten B, Staquet M, et al: Reporting results of cancer treatment. Cancer 47:207–214, 1981[CrossRef][Medline]

13. Barrett AJ: Annotation: Non-myeloablative stem cell transplants. Br J Haematol 111:6–17, 2000[CrossRef][Medline]

14. Du W, Dansey R, Abella EM, et al: Successful allogeneic bone marrow transplantation in selected patients over 50 years of age: A single institution’s experience. Bone Marrow Transplant 21:1043–1047, 1998[CrossRef][Medline]

15. Anasetti C: Transplantation of hematopoietic stem cells from alternate donors in acute myelogenous leukemia. Leukemia 14:502–504, 2000[Medline]

16. Schattenberg A, Schaap N, Preijers F, et al: Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant 26:17–22, 2000[CrossRef][Medline]

17. Runde V, deWitte T, Arnold R, et al: Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: Early transplantation with improved outcome—Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 21:255–261, 1998[CrossRef][Medline]

18. Sierra J, Storer B, Hansen JA, et al: Treatment of high-risk acute leukemia: The effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood 89:4226–4235, 1997[Abstract/Free Full Text]

19. Witherspoon RP, Deeg HJ, Storer B, et al: Hematopoietic stem-cell transplantation for treatment related leukemia or myelodysplasia. J Clin Oncol 19:2134–2141, 2001[Abstract/Free Full Text]

20. Deeg HJ, Appelbaum FR: Hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Leuk Res 24:653–663, 2000[CrossRef][Medline]

21. De la Rubia J, Saavedra S, Sanz GF, et al: Transplant-related mortality in patients older than 60 years undergoing autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 27:21–25, 2001[Medline]

22. De Witte T, Hermans J, Vossen J, et al: Haematopoietic stem cell transplantation for patients with myelodysplastic syndromes and secondary acute myeloid leukaemias: A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 110:620–630, 2000[CrossRef][Medline]

Submitted September 25, 2001; accepted January 23, 2003.

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