|Year : 2016 | Volume
| Issue : 2 | Page : 100-105
Effect of comorbidities on hematopoietic stem cell transplantation outcome in adult patients with different hematologic diseases: a single-center experience in Egypt
Amal M El Afifi1, Maha El Zemaity1, Nevine N Mostafa MD 1, Mohamed Moussa1, Gihan M Kamal1, Rasha Magdy1, Afaf Abdulaziz2, Nahela Shalaby2, Heba M Saber1
1 Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University Hospitals, Ain Shams University, Cairo, Egypt
2 Hematology Unit, Department of Clinical Pathology, Faculty of Medicine, Ain Shams University Hospitals, Ain Shams University, Cairo, Egypt
|Date of Submission||14-Oct-2015|
|Date of Acceptance||18-Oct-2015|
|Date of Web Publication||15-Jul-2016|
Nevine N Mostafa
Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University Hospitals, Ain Shams University, PO Box 11566, Cairo
Source of Support: None, Conflict of Interest: None
Background Hematopoietic stem cell transplantation (HSCT) is a procedure that can restore marrow function in patients who have had severe marrow injury. It is either autologous or allogeneic. It has become increasingly important to optimize pretransplant risk assessment to improve hematopoietic cell transplantation (HCT) decision making. Single-organ comorbidity involving the liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT. The HCT-comorbidity index (HCT-CI) has provided better prediction of HCT-related morbidity and mortality compared with other non-HCT-specific indexes.
Aim The aim of this study was to investigate the impact of various pretransplant comorbidities on the outcome of patients who had undergone either allogeneic or autologous HSCT in relation to treatment-related mortality, disease-related mortality, and overall survival.
Patients and methods A retrospective study was conducted at the Bone Marrow Transplantation Unit, Ain Shams University, on 119 patients who were transplanted either using autologous or allogeneic HSCT. All of them were older than 18 years and had different types of hematologic diseases. The most frequent hematologic disease was acute myeloid leukemia (34.4%), followed by multiple myeloma (17.6%), acute lymphoblastic leukemia (16.8%), and lymphoma (10.9%), whereas aplastic anemia, myelodysplastic syndrome, chronic myeloid leukemia, and biphenotypic leukemia collectively represented 20.1%. They were either incomplete or partial remission. They were categorized on the basis of the HCT-CI as follows: mild score (0), 43 (36.2%) patients; moderate score (1-2), 60 (50.4%) patients; and severe score (3), 16 (13.4%) patients. The study data were collected from medical notes, pathology reports, and laboratory data.
Results There was a statistically significant relation between the HCT-CI and overall survival (P = 0.012), disease-free survival (P = 0.007), mortality (P = 0.047), and the incidence of graft failure (P = 0.034).
Conclusion We concluded that the HCT-CI is a better predictor for detecting the influence of comorbidity in patients with hematologic disorders on mortality, overall survival, and disease-free survival after HCT.
Keywords: comorbidity index, hematopoietic stem cell transplantation, outcome
|How to cite this article:|
El Afifi AM, El Zemaity M, Mostafa NN, Moussa M, Kamal GM, Magdy R, Abdulaziz A, Shalaby N, Saber HM. Effect of comorbidities on hematopoietic stem cell transplantation outcome in adult patients with different hematologic diseases: a single-center experience in Egypt. Egypt J Haematol 2016;41:100-5
|How to cite this URL:|
El Afifi AM, El Zemaity M, Mostafa NN, Moussa M, Kamal GM, Magdy R, Abdulaziz A, Shalaby N, Saber HM. Effect of comorbidities on hematopoietic stem cell transplantation outcome in adult patients with different hematologic diseases: a single-center experience in Egypt. Egypt J Haematol [serial online] 2016 [cited 2019 Dec 11];41:100-5. Available from: http://www.ehj.eg.net/text.asp?2016/41/2/100/186414
| Introduction|| |
Hematopoietic stem cell transplantation (HSCT) is the intravenous infusion of hematopoietic stem and progenitor cells to restore normal hematopoiesis and/or treat malignancy. The term 'hematopoietic stem cell transplantation' has replaced the term 'bone marrow transplantation' (BMT) because hematopoietic stem cells can be derived from a variety of sources other than the bone marrow, including the peripheral blood and umbilical cord blood .
Despite the promises offered by this possibly life-saving treatment, there are risks associated with this procedure.
Patients undergoing BMT are at risk for granulocytopenia, impairment of barrier defenses, and impairment of cell-mediated immunity and humoral immunity. This impairment leads to an immunocompromised state, allowing microorganisms to cause infection more easily, even those with limited pathogenicity .
Those undergoing allogeneic transplantation are at a greater risk of infection because of a longer time for achieving engraftment (prolonged neutropenia) and the added risk for graft versus host disease (GVHD) .
It has become increasingly important to optimize pretransplant risk assessment to improve hematopoietic cell transplantation (HCT) decision making and clinical trial assignments.
Single-organ comorbidity involving the liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT .
A roadmap for maximization of the benefits of HCT would require novel approaches for both improving tumor control and lessening morbidity and mortality after HCT. It requires a better understanding of the biology and extents of interactions between HCT-associated interventions and patient-specific risk factors. This would allow for accurate pretransplant benefit-risk assessment leading to assignments of patients to the most tolerable modality of HCT .
The HCT-comorbidity index (CI) was established specifically to predict the influence of comorbidity on patients with hematologic disorders, whereas the Charlson Comorbidity Index (CCI) is a general scoring system for comorbidity in various disease conditions. The new HCT-CI consisted of 17 comorbidities, including three comorbidities that were not represented in the CCI - obesity, peritransplant infections, and psychiatric disturbances (with different integer weights between 1 and 3 assigned to each) . It was found that the HCT-CI score was more representative of the patient cohort considered for a transplant and provided a better assessment of nonrelapse mortality (NRM) and overall survival risks compared with the original CCI .
The HCT-CI score was developed based on 1055 patients treated with various nonmyeloablative (n = 294) or ablative (n = 761) conditioning regimens in a single institution, Fred Hutchinson Cancer Research Center (FHCRC).
| Patients and methods|| |
The study included 119 patients who underwent either allogeneic or autologous BMT at our Stem Cell Transplant Unit, Ain Shams University Hospitals, between April 2005 and February 2014. They were adult patients older than 18 years with different hematologic diseases (malignant or nonmalignant) who underwent HSCT. All patients received myeloablative.
Conditioning regimens included busulfan/fludarabine (Bu/Flu) (40 patients; 33.6%), busulfan/Cyclophosphamide (Bu/CTX) (19 patients; 16%), total body irradiation/Cyclophosphamide (TBI/CTX) (12 patients; 10.1%), high-dose melphalan (23 patients; 19.3%), and other protocols (25 patients; 21%).
All patients gave their informed consent to the planned treatment schedule.
Antibiotics were routinely administered as prophylaxis against bacterial (ciprofloxacin), fungal (fluconazole), Pneumocystis jiroveci (trimethoprim and sulfamethoxazole), and herpes virus (acyclovir) infections. Early detection of cytomegalovirus antigenemia by screening once weekly and preemptive ganciclovir therapy, in patients with early signs of reactivation, were routinely performed in all patients.
All relevant investigations were performed within the routine workup for transplant. Data were extracted from the medical records as well as laboratory values at the time of transplant. They were retrospectively analyzed. Comorbidities of each patient were scored according to the HCT-CI on the worksheet .
Analysis of data was carried out with IBM computer using statistical package for the social sciences (SPSS, version 12; SPSS Inc., Chicago, Illinois, USA) as follows:
- Descriptive data of qualitative variables were presented as number and percentage.
- The χ2 -test was used to compare qualitative data of quantitative variables.
- The unpaired t-test was used to compare two groups as regards quantitative variables.
- The correlation coefficient test was used to rank different variables positively or inversely versus each other.
A P value greater than 0.05 was considered insignificant. A P value less than 0.05 was considered significant. A P value less than 0.01 was considered highly significant.
| Results|| |
This retrospective study was conducted on 119 patients who underwent BMT in the Stem Cell Transplant Unit, Ain Shams University, from April 2005 to February 2014. This study included 72 (60.5%) male and 47 (39.5%) female patients. All patients were older than 18 years with hematologic diseases (malignant or nonmalignant) who underwent allogeneic (matched or mismatched-related) (82 patients; 68.9%) or autologous HSCT (37 patients; 31.1%). All patients received myeloablative conditioning regimens, including Bu/Flu (40 patients; 33.6%), Bu/CTX (19 patients; 16%), TBI/CTX (12 patients; 10.1%), high-dose melphalan (23 patients; 19.3%), and other protocols (25 patients; 21%). They were divided on the basis of disease diagnosis into five groups:
- Acute leukemia (63 patients; 53%): acute myeloid leukemia (AML), 41 patients; T Acute lymphoblastic leukemia (TALL), 11 patients; pre-B Acute lymphoblastic leukemia (BALL), nine patients; and acute biphenotypic leukemia, two patients.
- Lymphomas (13 patients; 11%): Hodgkin's lymphoma (eight patients) and non-Hodgkin's lymphoma (five patients).
- BM aplasia/myelodysplastic syndrome (MDS) (16 patients; 13.4%): aplastic anemia (12 patients) and MDS (four patients).
- Chronic myeloid leukemia (CML) (six patients; 5%): one of them had chronic myelofibrosis in addition to CML. CML patients were transplanted before the introduction of tyrosine kinase inhibitor drugs in our unit.
- Multiple myeloma (21 patients; 17.6%).
All patients were categorized on the basis of the HCT-CI  into three groups: low risk (score 0), 36.2%; intermediate risk (score 1-2), 50%; and high risk (score ≥3), 13.8%.
After a follow-up period of minimum of 10 months and maximum of 112 months, 54/119 (45.4%) patients died [11 (9.2%) patients died from disease relapse and 43 (36.2%) deaths were due to NRM], with an overall survival of 52.1% (62 patients) and three (2.5%) patients were lost to follow-up.
[Table 1] shows a statistically significant difference between patients who underwent autologous, fully matched related allogeneic and mismatched related allogeneic HSCT as regards post-transplant mortality.
|Table 1 Comparison between the type of hematopoietic cell transplantation as regards post-transplant mortality using the χ2-test |
Click here to view
[Table 2] shows a statistically significant difference between mild, moderate, and severe HCT-CI score as regards post-transplant mortality.
|Table 2 Comparison between different hematopoietic cell transplantation-comorbidity index scores as regards post-transplant mortality using the χ2-test |
Click here to view
[Table 3] shows a highly statistically significant difference between the eight groups of patients with different diagnoses as regards the HCT-CI score.
|Table 3 Comparison between different disease diagnoses as regards hematopoietic cell transplantation-comorbidity index score the using χ2-test |
Click here to view
[Table 4] shows a statistically significant difference between mild, moderate, and severe HCT-CI scores as regards the incidence of graft failure ([Table 5] and [Figure 1] and [Figure 2]).
|Figure 1 Comparison between patients with mild, moderate, and severe hematopoietic cell transplantation-comorbidity index scores as regards overall survival with a statistically significant difference|
Click here to view
|Figure 2 Comparison between different disease statuses as regards disease-free survival after transplant with no statistically significant difference|
Click here to view
|Table 4 Comparison between different hematopoietic cell transplantation-comorbidity index scores as regards the incidence of graft failure using the χ2-test |
Click here to view
|Table 5 The number of patients transplanted every year and annual number of mortality included in our study |
Click here to view
| Discussion|| |
Allogeneic HCT is an integral part of postremission therapy in adult patients with malignant diseases who present with high-risk features. Although HCT has considerable curative potential in these situations, its application is limited by transplant-related complications such as infections and GVHD, which can lead to mortality rates of up to 50% in older or less-fit patients .
A balanced risk-benefit approach to HCT is the key for maximized chances of cure with acceptable quality of life for patients with advanced hematologic malignancies. Single-organ comorbidity involving the liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT . This leads to the development of the HCT-CI .
The present study was a retrospective study designed to assess the effect of pretransplantation comorbidities on the outcome of HCT, including morbidity and mortality, with special emphasis on overall survival.
This study was conducted in the Transplantation Unit, Ain Shams University Hospital. All patients who underwent allogeneic or autologous HSCT from April 2005 to February 2014 were recruited. It included 119 patients irrespective of the underlying disease and the conditioning regimen. A total of 82 patients underwent allogeneic HSCT and 37 patients underwent autologous HSCT.
In the present study, patient ages ranged from 18 to 59 years, with a median age of 27 years. The patients were divided into two groups based on age: patients younger than 40 years (78 patients) and patients older than 40 years (41 patients). There was no statistically significant difference between the two age groups as regards overall survival and mortality. Similar results were reported by Keating et al. . Moreover, Slack et al.  studied 100 patients with a median age of 56 years with similar results as regards overall survival and mortality.
The most frequent hematologic disease was AML (41 patients; 34.4%), followed by multiple myeloma (n = 21; 17.6%), acute lymphoblastic leukemia (n = 20; 16.8%), and lymphoma (n = 13; 10.9%), whereas aplastic anemia, MDS, CML, and acute biphenotypic leukemia patients collectively represented only 24 patients (20.1%).
As regards disease diagnosis, the highest mortality was reported in patients with aplastic anemia, followed by acute leukemia, and the least mortality was reported in patients with lymphomas. However, there was no statistically significant difference between different disease diagnoses as regards mortality. Similar results were reported by Chemnitz et al. , who found that mortality is not related to disease diagnosis.
There was a statistical difference between autologous HCT, allogeneic matched related and mismatched related HCT as regards mortality and overall survival. The highest mortality was in mismatched related allogeneic HCT (only one case), followed by fully matched allogeneic at the same time. The least overall survival was reported in mismatched related allogeneic, followed by autologous HCT and matched allogeneic HCT. Similar results were reported by Keating et al. , who found that autologous HCT in AML is associated with low NRM. Similar results were also reported by multiple studies in which matched related allogeneic HCT significantly reduces the risk for disease relapse, but increased the risk for NRM.
The patients were classified into three groups based on their HCT-CI score: low risk (score 0), 36.2%; intermediate risk (score 1-2), 50%; and high risk (score ≥3), 13.8%. Hepatic, pulmonary, and obesity comorbidities were the most commonly observed association within our study group.
Hepatic comorbidity was the most commonly observed association in our study group due to recurrent blood transfusion and high prevalence of hepatitis C virus (HCV) in Egypt. HCV infection before HCT was not associated with a statistically significant impact on mortality but had a significant impact on overall survival (P = 0.017). Similar results were reported in Chemnitz et al.  as regards mortality but not overall survival. However, Ramos et al.  reported that patients with evidence of HCV infection before allogeneic HSCT had worse overall survival and NRM compared with seronegative controls.
There was no statistically significant difference between patients with mild, moderate, and high HCT-CI as regards the incidence of acute and chronic GVHD after transplant. This is contradictory to the results reported by Sorror et al. , in which HCT-CI score had a significant prognostic effect on the incidence of acute GVHD. This may be due to the small number of patients included in our study and different types of transplantation included in our study.
In our study, the incidence of graft failure was 5.9%. There was a statistically significant impact of HCT-CI score on the incidence of graft failure after transplant and subsequently the incidence of graft failure had a statistically significant impact on mortality.
There was no statistically significant impact of HCT-CI score on the development of bacterial infection, viral infection, and fungal infection in our study. To the best of our knowledge, there are no available studies on this subject.
In summary, this study has got a significant relevance as it provides a prognostic tool for evaluation of patients before transplant and for the prediction of the results after transplant to minimize mortality and morbidity in patients undergoing HSCT.
Therefore, the HCT-CI score is a significant prognostic risk factor for mortality, overall survival, and disease-free survival in patients before transplant.
| Conclusion|| |
The HCT-CI has established itself in this setting as a reliable tool to predict outcome following HSCT. Our retrospective study confirms the role of HCT-CI to predict overall survival, mortality, and disease-free survival of the transplant patients. Moreover, the HCT-CI score was shown to be directly associated with the incidence of graft failure after.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science
Tomblyn M, Chiller T, Einsele H, et al.
Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant
Sorror ML. Comorbidities and hematopoietic cell transplantation outcomes. Hematology Am soc Hematal Educ Program
Lowsky R, Negrin RS. Principles of hematopoietic cell transplantation [chapter 21]. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, editors. Williams hematology
. 8th ed. USA: McGraw-Hill Education; 2012. 313-343.
Castagna L, Fürst S, Marchetti N, et al.
Retrospective analysis of common scoring systems and outcome in patients older than 60 years treated with reduced-intensity conditioning regimen and alloSCT. Bone Marrow Transplant
Chemnitz JM, Chakupurakal G, Bäßler M, et al.
Pretransplant comorbidities maintain their impact on allogeneic stem cell transplantation outcome 5 years posttransplant: a retrospective study in a single German institution. ISRN Hematol
:853435. Available at: http://dx.doi.org/10.1155/2014/853435
Sorror ML, Maris MB, Storb R, et al.
Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood
Terwey TH, Kim TD, Arnold R. Allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia. Curr Hematol Malig Rep
Keating A, DaSilva G, Pérez WS, et al.
Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Hematologica
Slack JL, Dueck AC, Fauble VD, et al.
Reduced toxicity conditioning and allogenic stem cell transplantation in adults using fludarabine, BCNU, melphalan, and antithymocyte globulin (FBM-A): outcomes depend on disease risk index but not age, comorbidity score, donor type, or HLA mismatch. Biol Blood Marrow Transplant
Ramos CA, Saliba RM, Pádua L, et al.
Impact of hepatitis C virus seropositivity on survival after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Haematologica
Sorror ML, Martin PJ, Storb RF, et al.
Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]