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Table of Contents
CASE REPORT
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 193-196

Allogeneic hematopoietic stem cell transplantation in a 76-year-old woman with relapsed acute myeloid leukemia


Division of Hematology and Medical Oncology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Date of Submission24-May-2019
Date of Decision26-Jun-2019
Date of Acceptance18-Jul-2019
Date of Web Publication22-Nov-2019

Correspondence Address:
Dr. Pei-Ying Hsieh
Division of Hematology and Medical Oncology, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S. Road, Banciao Dist., New Taipei City 220
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCRP.JCRP_15_19

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  Abstract 


Acute myeloid leukemia (AML) is commonly diagnosed in the elderly. Treatment of AML frequently requires hematopoietic stem cell transplantation (HSCT), which is associated with significant treatment-related toxicity and is considered to be too intense for older patients. However, with the development of reduced intensity conditioning, patients of increasing age are now considered for HSCT. We present a case of relapsed AML in a 76-year-old woman who was successfully treated with allogeneic stem cell transplantation. She endured the process without significant complications and achieved a durable treatment response, demonstrating the feasibility of allogeneic HSCT in patients with very advanced age.

Keywords: Acute myeloid leukemia, reduced intensity conditioning, stem cell transplantation


How to cite this article:
Lee KY, Hsieh PY. Allogeneic hematopoietic stem cell transplantation in a 76-year-old woman with relapsed acute myeloid leukemia. J Cancer Res Pract 2019;6:193-6

How to cite this URL:
Lee KY, Hsieh PY. Allogeneic hematopoietic stem cell transplantation in a 76-year-old woman with relapsed acute myeloid leukemia. J Cancer Res Pract [serial online] 2019 [cited 2019 Dec 5];6:193-6. Available from: http://www.ejcrp.org/text.asp?2019/6/4/193/271495




  Introduction Top


Acute myeloid leukemia (AML) is predominantly diagnosed in the elderly, with a median age at diagnosis of 72 years.[1] AML in the elderly is characterized by distinct biological properties associated with an adverse prognosis, including a higher percentage of leukemic cell treatment resistance and an increased number of high-risk features.[2],[3] In the general population, hematopoietic stem cell transplantation (HSCT) is often considered in the setting of disease with these high-risk features. However, in elderly patients, physicians are often reluctant to choose intensive treatment, and hence, elderly patients seldom receive hematopoietic cell transplantation (HCT) due to concerns over toxicity.[4]

With the development of reduced intensity conditioning (RIC), the proportion of older patients with AML receiving HSCT have steadily increased in the past decade.[5] Considerable evidence has shown the favorable effect of RIC in this population, with tolerable toxicity, successful engraftment, and relatively favorable outcomes.[6],[7],[8] Furthermore, several recent publications have investigated the impact of age on outcomes of HSCT in the setting of RIC and found that increased age alone had no significant negative impact on overall survival (OS) and nonrelapse mortality (NRM).[9],[10],[11] In view of these findings, considering HSCT is warranted in selected patients even with very advanced age. Herein, we report a 76-year-old woman with AML who received RIC and HSCT following the reinduction of relapsed disease, which resulted in successful engraftment and durable remission. To the best of our knowledge, she is the oldest patient to have received an allogeneic HSCT in Taiwan to date.


  Case Report Top


A 76-year-old woman with a medical history of diabetes mellitus and hypertension presented with dry cough and sore throat for 2 months. Additional symptoms included general malaise, fatigue, and poor appetite. She initially sought help at a local clinic and was given steroids and empirical antibiotics. Despite this treatment, her symptoms persisted and she was subsequently referred to a tertiary medical center for further evaluation.

A physical examination revealed purpura on bilateral forearms, and a hemogram revealed white blood cell: 2060/μL, platelet: 43,000/μL, hemoglobin: 7.8 g/dL, neutrophil: 6%, lymphocytes: 51%, monocytes: 6%, blasts: 15%, and atypical lymphocytes: 12%. Renal and liver function tests, coagulation tests, and electrolytes were within normal range. Bilateral ground glass–like infiltration over the lower lungs was visible on a chest X-ray, and a subsequent chest computed tomography showed multiple consolidation over bilateral lower lungs. Fungal pneumonia was suspected, and she was admitted to receive intravenous antibiotic/antifungal treatment and to undergo evaluation for pancytopenia.

Bone marrow aspiration smear revealed hypercellularity with abundant blasts [Figure 1], and bone marrow biopsy showed a high proportion of blasts without differentiating features. Cytogenetics demonstrated a normal karyotype, and multicolor flow cytometry identified blasts with positive CD34/HLA-DR/CD13/CD33/partial CD15/cytoplasmic myeloperoxidase, confirming the diagnosis of AML, French-American-British classification M1. She was categorized as being at intermediate risk, according to the European Leukemia Net (ELN) risk stratification.
Figure 1: Bone marrow studies at different stages of the patient's treatment course: (a) initial diagnosis, (b) first remission, (c) recurrence before transplantation, and (d) after transplantation

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The patient then received induction chemotherapy with “I3A7” following adequate infection control. She endured induction chemotherapy despite the subsequent confirmation of invasive pulmonary aspergillosis and went into complete remission. The fungal pneumonia was managed successfully with micafungin and later posaconazole.

The patient then underwent four cycles of high-dose cytarabine consolidation, and follow-up flow cytometry showed residual leukemic cells. Gross relapse occurred 6 months following completion of consolidation therapy with the onset of refractory pancytopenia.

With a fair performance status, relatively low comorbidity, good tolerance to previous treatment, and a strong personal preference for curative treatment, intensive therapy was considered. More specifically, her HCT-specific comorbidity index (HCT-CI) was 2 and Karnofsky performance status was 90, inferring a relatively low transplant-related risk. Hence, she received reinduction with the “FLAG” regimen, and a search for potential allogeneic stem cell donors was undertaken. An HLA fully matched sibling donor was identified (her 60-year-old sister) with an obstetric history of G2P2A0 [Table 1]. The patient successfully went into second complete remission after reinduction, and an allogeneic stem cell transplantation was arranged. A RIC regimen was designed for the patient with fludarabine, busulfan, and cyclophosphamide (fludarabine 30 mg/m2 × 5 days, busulfan 3.2 mg/kg × 2 days, and cyclophosphamide 30 mg/kg × 1 day). A stem cell dose of 6.46 × 106/kg was infused, and antithymocyte immunoglobin 2.5 mg/kg was administered on day 2 (D2) to D1. Graft-versus-host disease (GVHD) prophylaxis included daily cyclosporine infusion (3 mg/kg) initiated from D1, adjusted according to the trough level, and methotrexate infusion on D1, D3, D6, and D11 (15 mg/m2 for D1 and 10 mg/m2 for D3, D6, and D11). She tolerated the regimen well with no significant infection during the neutropenic stage and only Grade I diarrhea and fatigue during the course. Successful engraftment was achieved on D11, and no GVHD was observed up to D119. Follow-up flow cytometry and bone marrow aspiration smear confirmed successful trilineage engraftment with no residual disease. The standard short tandem repeat genotyping analysis showed complete chimerism.
Table 1: Donor and recipient characteristics

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  Discussion Top


The treatment of AML in older patients has undergone rapid changes in the past decade. Earlier studies repeatedly reported that increasing age was a significant risk factor for worse outcomes after HCT in patients with AML,[12],[13] which led to the adoption of age restrictions for HSCT in the earlier AML treatment guidelines. However, with the higher incidence of AML in patients in the latter decades of life and the worse prognosis in elderly AML patients, such age restrictions severely limited the treatment options for these patients.

With the advent of RIC regimens, HSCT has been extended to an increasingly older population, and the median age of patients with myelodysplastic syndrome or AML who have received HSCT has increased by 20 years since the 1980s.[10] In a meta-analysis by Rashidi et al., the outcomes of HSCT with RIC in elderly patients in 13 studies were analyzed.[14] The pooled analysis showed a 3-year relapse-free survival rate of 35% in patients over 60 years of age, suggesting that RIC is a viable treatment option in older patients with AML. Several retrospective analyses have demonstrated that increased age alone was not associated with worse NRM or OS, further challenging the use of age alone as a criterion in patient selection.[9],[11],[13]

Many of the aforementioned studies that explored the impact of age on HSCT outcomes in AML patients selected patients older than 60 or 65 years of age;[9],[11],[14] however, data on AML patients older than 70 years receiving HSCT in the setting of RIC are more limited. Several recent studies have addressed this issue and examined the outcomes of HSCT in hematological malignancies in patients over 70 years of age, and the results have been consistent with younger populations with a 2-year progression-free survival of 32%–39%.[15],[16] This suggests that selected patients over 70 years of age with hematological malignancies should also be considered for HSCT.

Taken together, these findings highlight the relevance of patient selection for HCT in the elderly. Several tools have been developed to stratify the risk of transplantation and evaluate the suitability of patients for HSCT, including the HCT-CI scoring system which is used to predict transplant-related toxicity and is now frequently used for the pretransplant assessment.[17] However, the HCT-CI is insufficient with regard to incorporating all relevant parameters in elderly patients. Consequently, several trials have investigated the prognostic significance of geriatric assessment in this scenario, which encompassed assessment of frailty, cognition, function status, nutrition, and socioeconomic status, all of which may ultimately impact the patient's outcome.[18],[19] The potential use of geriatric assessment scales in guiding patient selection for HCT in the elderly appears to be promising; however, further validation is required.

Our case was a 76-year-old woman who received HCT with RIC after the reinduction of relapsed AML. She endured the transplantation process without significant complications or GVHD and resulted in fair disease control. In summary, this case underscores the feasibility of HCT in selected patients with very advanced age (>70 years) and its potential benefit for these patients. HCT should be considered and evaluated in all indicated AML patients regardless of age.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Juliusson G, Lazarevic V, Hörstedt AS, Hagberg O, Höglund M; Swedish Acute Leukemia Registry Group. Acute myeloid leukemia in the real world: Why population-based registries are needed. Blood 2012;119:3890-9.  Back to cited text no. 1
    
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Menzin J, Lang K, Earle CC, Kerney D, Mallick R. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med 2002;162:1597-603.  Back to cited text no. 2
    
3.
Mohammadi M, Cao Y, Glimelius I, Bottai M, Eloranta S, Smedby KE. The impact of comorbid disease history on all-cause and cancer-specific mortality in myeloid leukemia and myeloma – A Swedish population-based study. BMC Cancer 2015;15:850.  Back to cited text no. 3
    
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Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: A population-based study. Haematologica 2012;97:1916-24.  Back to cited text no. 4
    
5.
Sengsayadeth S, Savani BN, Blaise D, Malard F, Nagler A, Mohty M. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission – A review from the acute leukemia working party of the EBMT. Haematologica 2015;100:859-69.  Back to cited text no. 5
    
6.
Ringdén O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N, et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 2009;27:4570-7.  Back to cited text no. 6
    
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Kurosawa S, Yamaguchi T, Uchida N, Miyawaki S, Usuki K, Watanabe M, et al. Comparison of allogeneic hematopoietic cell transplantation and chemotherapy in elderly patients with non-M3 acute myelogenous leukemia in first complete remission. Biol Blood Marrow Transplant 2011;17:401-11.  Back to cited text no. 7
    
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Farag SS, Maharry K, Zhang MJ, Pérez WS, George SL, Mrózek K, et al. Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant 2011;17:1796-803.  Back to cited text no. 8
    
9.
Aoki J, Kanamori H, Tanaka M, Yamasaki S, Fukuda T, Ogawa H, et al. Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia. Am J Hematol 2016;91:302-7.  Back to cited text no. 9
    
10.
Kröger N. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood 2012;119:5632-9.  Back to cited text no. 10
    
11.
McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol 2010;28:1878-87.  Back to cited text no. 11
    
12.
Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic leukemia working party of the European group for blood and marrow transplantation. Lancet 1998;352:1087-92.  Back to cited text no. 12
    
13.
Sorror ML, Storb RF, Sandmaier BM, Maziarz RT, Pulsipher MA, Maris MB, et al. Comorbidity-age index: A clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol 2014;32:3249-56.  Back to cited text no. 13
    
14.
Rashidi A, Ebadi M, Colditz GA, DiPersio JF. Outcomes of allogeneic stem cell transplantation in elderly patients with acute myeloid leukemia: A systematic review and meta-analysis. Biol Blood Marrow Transplant 2016;22:651-7.  Back to cited text no. 14
    
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Heidenreich S, Ziagkos D, de Wreede LC, van Biezen A, Finke J, Platzbecker U, et al. Allogeneic stem cell transplantation for patients age≥70 years with myelodysplastic syndrome: A retrospective study of the MDS subcommittee of the chronic malignancies working party of the EBMT. Biol Blood Marrow Transplant 2017;23:44-52.  Back to cited text no. 15
    
16.
Muffly L, Pasquini MC, Martens M, Brazauskas R, Zhu X, Adekola K, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood 2017;130:1156-64.  Back to cited text no. 16
    
17.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT. Blood 2005;106:2912-9.  Back to cited text no. 17
    
18.
Muffly LS, Kocherginsky M, Stock W, Chu Q, Bishop MR, Godley LA, et al. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica 2014;99:1373-9.  Back to cited text no. 18
    
19.
Deschler B, Ihorst G, Schnitzler S, Bertz H, Finke J. Geriatric assessment and quality of life in older patients considered for allogeneic hematopoietic cell transplantation: A prospective risk factor and serial assessment analysis. Bone Marrow Transplant 2018;53:565-75.  Back to cited text no. 19
    


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