- Email: [email protected]
No Evidence for Particular Association Between HLA-Haploidentical Hematopoietic Stem Cell Transplantation and Psychological Distress
No Evidence for Particular Association Between HLA-Haploidentical Hematopoietic Stem Cell Transplantation and Psychological Distress Rie Akahoa,*, Akiko Otsub, Aiko Igarashic, Yuko Aokib, Takaubu Takemurad, Sayaka Kobayashia,e, Kazuteru Ohashic, and Katsuji Nishimuraa a Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; bDepartment of Psycho-Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; cDepartment of Hematology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; dDepartment of Psychology for Human Well-being, Faculty of Comprehensive Welfare, Tohoku Fukushi University, Sendai, Japan; and eDepartment of Psychiatry, Saitama Medical University Saitama Medical Center, Saitama, Japan
ABSTRACT Background. The psychological distress experienced by patients scheduled for hematopoietic stem cell transplantation (HSCT) is of clinical concern. However, distress experienced by patients scheduled for HLA-haploidentical HSCT vs that of patients scheduled for other types of matched HSCT is unknown. We conducted a retrospective study to clarify whether the type of HSCT influences the appearance of psychological distress in patients anticipating HSCT. Methods. One hundred fifty-seven patients who had undergone any of 4 types of HSCT at Tokyo Metropolitan Komagome Hospital between October 2013 and September 2016 and had completed the Profile of Mood States (POMS) questionnaire within 2 weeks before the procedure were included. We computed T-scores for the tension-anxiety (TA) and depression (D) subscales, took scores 60 to represent mood disturbance of clinical concern, and examined scores and other clinical variables in relation to each procedure. Results. Twenty-two (14.0%) patients had a POMS-TA score 60, and 26 (16.6%) had a POMS-D score 60. The numbers of POMS-TA and POMS-D scores 60 did not differ significantly with respect to age, sex, leukemia type, number of previous transplants, disease status, comorbidity index, or transplant type. A multivariate logistic regression analysis confirmed the absence of an influence of the type of HSCT on the incidence of POMSTA or POMS-D scores 60. Conclusion. Attention should be paid to the matter of psychological distress in patients with leukemia who will be treated by HSCT, even HLA-haploidentical HSCT. Such patients need psychological support, especially during the waiting period immediately prior to the transplantation procedure.
H
EMATOPOIETIC stem cell transplantation (HSCT) is potentially curative in patients with leukemia. Until the 1990s, the potential for anxiety and depression in patients undergoing HSCT was a matter of great concern [1,2], especially because it was generally understood that possible complications such as infections and graft-versus-host disease (GVHD) were not well controlled. Since the early 2000s, advances in transplantation medicine, including infection control, have reduced patients’ physical distress, and various interventions have been introduced to alleviate
0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.03.029
1990
the psychological distress associated with HSCT [3]. Nevertheless, psychological distress remains a matter of concern for patients scheduled for HSCT [4].
*Address correspondence to Rie Akaho, MD, PhD, Department of Psychiatry, Tokyo Women’s Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: akaho.rie@ twmu.ac.jp ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 1990e1993 (2019)
HLA-HAPLOIDENTICAL HEMATOPOIETIC STEM CELL
Currently, 4 types of HSCT are practiced. The first is human leukocyte antigen (HLA)-matched related donor (MRD) HSCT. An MRD is the most suitable donor for HSCT, but an MRD exists in only about 30% of cases [5,6]. The second is HLA-matched unrelated donor (MUD) HSCT, which means that HLA-matched bone marrow is obtained from a bone marrow bank [7]. The third is umbilical cord blood HSCT (CBT), which means that cord blood is obtained for transplantation, and the fourth is HLA-haploidentical HSCT (haplo-HSCT), which means that the transplant material is obtained from a halfmatched donor. This method is especially useful when finding a suitable donor becomes a long-drawn-out procedure. Haplo-HSCT has been problematic in terms of both GVHD and rejection, the risks of which are high in comparison to those associated with matched transplantation. Progress in transplantation medical care, however, led to widespread use of haplo-HSCT, beginning around 2013 [5,8,9]. Haplo-HSCT is considered the treatment of choice for patients for whom matched donor transplantation is not possible. The physical distress of these patients in comparison to that of matched donor recipients is well known, but there is no report regarding the psychological distress experienced by haplo-HSCT recipients vs that of matched transplant recipients. We conducted the retrospective comparative study described herein to clarify whether the type of HSCT influences the appearance of psychological distress in patients expecting to undergo HSCT. The study was conducted at Tokyo Metropolitan Komagome Hospital, which pioneered research on haplo-HSCT in Japan. MATERIALS AND METHODS Study Patients We included in the study all 157 patients who underwent HSCT for leukemia at Tokyo Metropolitan Komagome Hospital between October 1, 2013 and September 30, 2016. The patients were identified from departmental records, and the study was approved by the Ethics Committee of Tokyo Metropolitan Komagome Hospital (approval no. 2174).
Study Variables We obtained the following data from patients’ clinical records: age, sex, leukemia type, number of previous transplants, disease status, hematopoietic cell transplantationespecific comorbidity index (HCT-CI), and transplant type. Age was categorized as 10 to 39 years, 40 to 59 years, or 60 years or more. The disease itself was classified as acute myelogenous (myeloid) leukemia or acute lymphoblastic (lymphoid) leukemia. Disease status was classified as first or second complete remission (for which the post-transplant prognosis is generally good) or other (ie, primary induction failure, partial remission, or third complete remission [for which the post-transplant prognosis is generally poor]). HCT-CIs range from 0 to 5 and are used to classify comorbidities that might affect a patient’s risk of death. When there are no comorbidities, the HCT-CI is 0; when the HCT-CI is 3 or more, the patient’s risk of death from a comorbidity is quite high [10].
1991
Assessment of Psychological Distress Approximately 2 weeks before performance of the HSCT procedure, each patient had been asked, as a matter of routine, to complete the Profile of Mood States (POMS) questionnaire, which is a validated self-report psychological inventory used to assess transient feelings and mood states. POMS, widely used in Western countries and translated into Japanese, measures 6 mood states: tension-anxiety, depressiondejection, anger-hostility, vigor, fatigue, and confusion. Thus, in addition to the clinical variables noted, we obtained patients’ POMS scores, focusing on 2 subscales: the tension-anxiety (POMS-TA) subscale, a 9-item subscale with scores ranging from 0 to 36, and the depression-dejection (POMS-D) subscale, a 15-item subscale with scores ranging from 0 to 60. We obtained scores from the patients’ records, and we computed individual T scores for each of the 2 subscales, with a T score of 60 (SD 1) or more taken to represent a greater-than-expected mood disturbance.
Statistical Analysis Age, sex, leukemia type, number of previous transplants, disease status, HCT-CI, and HSCT type were examined in relation to POMS-TA scores (<60 vs 60) and in relation to POMS-D scores (<60 vs 60), and differences were analyzed using the c2 test. A logistic regression analysis was then performed to analyze the influence of HSCT type on POMS-TA and POMS-D scores, with adjustment made for age, sex, leukemia type, number of previous transplants, and HCT-CI. All statistical analyses were performed with SPSS version 20, and P < .05 was accepted as statistically significant.
RESULTS Patient Characteristics
The characteristics of the 157 study patients are shown in Table 1. Patients ranged in age from 18 to 70 years, with a mean age of 47.9 13.5 years. The male:female ratio was 105:52. All 4 types of transplant were performed among this group of patients: HLA-MRD HSCT in 26 patients, HLAMUD HSCT in 76, CBT in 19, and haplo-HSCT in 36. Psychological Distress
Thirty (19.1%) of the 157 patients reported psychological distress at or above the threshold level, with 22 (14.0%) having a POMS-TA score 60, 26 (16.6%) having a POMSD score 60, and 18 (11.5%) having both POMS-TA and POMS-D scores 60. Relation Between Psychological Distress and HSCT Type
The numbers of POMS-TA and POMS-D scores 60 did not differ significantly in relation to age, sex, leukemia type, number of previous transplants, disease status, HCT-CI, or transplant type. Multivariate logistic regression analysis confirmed the absence of an influence of the type of HSCT on the occurrence of POMS-TA scores 60, with odds ratios for such scores related to MRD, MUD, and CBT (vs haploHSCT) of 1.664, 1.746, and 1.92, respectively (Table 2). Multivariate logistic regression analysis also confirmed the absence of an influence of the type of HSCT on POMS-D scores 60 (with odds ratios of 1.11, 0.725, and 0.739, respectively) (Table 2).
1992
AKAHO, OTSU, IGARASHI ET AL
Table 1. Clinical Characteristics of the Patients Included in the Study (N [ 157) Variable
No. of Patients
Age Range (y) 10e39 40e59 60 Sex Male Female Leukemia Type AML ALL/LBL Disease Status First or second CR Other HCT-CI 0 1e2 3 No. of Previous Transplants 0 1 2 Type of HSCT Haplo Matched related Matched unrelated CBT
39 77 41 105 52 101 56 98 59 77 47 33 142 14 1 36 26 76 19
Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; CR, complete remission; CBT, umbilical cord blood HSCT; Haplo, HLAhaploidentical HSCT; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HSCT, hematopoietic stem cell transplantation; LBL, lymphoblastic lymphoma; Matched related, HLA-matched related HSCT; Matched unrelated, HLA-matched unrelated HSCT; Other, primary induction failure, partial remission, or third complete remission.
DISCUSSION
In this study, we focused on the potential for psychological distress experienced by patients expecting to undergo haploHSCT, a relatively new type of HSCT. We are particularly Table 2. Relations Between Presence of Psychological Distress (Shown by POMS-TA and POMS-D) and Type of HSCT POMS-TA 60 Haplo Matched related Matched unrelated CBT POMS-D 60 Haplo Matched related Matched unrelated CBT
OR*
95% CI
P Value
(reference) 1.664 1.746 1.92
0.320e8.654 0.428e7.116 0.323e11.395
.545 .437 .473
(reference) 1.11 .725 .739
0.284e4.338 0.220e2.386 0.149e3.677
.881 .596 .712
Abbreviations: CBT, umbilical cord blood HSCT; CI, confidence interval; Haplo, haploidentical HSCT; HCT-CI, hematopoietic cell transplantationspecific comorbidity index; HSCT, hematopoietic stem cell transplantation; Matched related, HLA-matched related HSCT; Matched unrelated, HLAmatched unrelated HSCT; OR, odds ratio; POMS-D, Profile of Mood Statesdepression-dejection subscale; POMS-TA, Profile of Mood States-tensionanxiety subscale. *Adjusted for age, sex, leukemia type, number of previous transplants, and HCT-CI.
interested in any psychological distress associated with haploHSCT compared with that associated with MRD, MUD, and CBT because haplo-HSCT is used especially for patients for whom donor coordination or the patient’s condition make other options unrealistic. We found patients’ psychological stress levels to be similar, regardless of the type of HSCT planned. We evaluated our study results from 2 standpoints. First, we asked ourselves how well the patients understood and recognized the difference between haplo-HSCT and other transplant methods. For informed consent before transplantation, various support systems have been advanced to help patients understand the information provided and make decisions [11,12]. At Tokyo Metropolitan Komagome Hospital, information is provided in booklet form. The important information is explained in simple terms and the booklets are easy to read. For patients who will undergo haplo-HSCT, we use the same booklet we use for other patients who will undergo HLA-matched transplantation and explain the likelihood of GVHD and the need for highdose immunosuppressive agents. The information is provided in such a way as to alleviate patients’ sense of fear. Second, we asked ourselves about the timing of the psychological distress. Patients scheduled to undergo haplo-HSCT may have experienced stress for a fairly long period of time preceding the decision to perform haplo-HSCT. These patients might have searched for and not found an MRD or MUD and thus experienced the stress of uncertainty during the decision-making period. The POMS questionnaire was administered within a short 2-week period before transplantation (and after the type of transplant had been decided), so any psychological distress experienced by patients early during the decision-making process would not have been detected. We can assume, however, that the psychological state of patients already scheduled for haplo-HSCT, despite the known difficulties, is similar to that of patients scheduled for other types of transplant. We recognize that our study results should be interpreted in light of the study limitations, which include that fact that socioeconomic factors that might have influenced patients’ distress levels, such as the presence vs absence of family support and employment, were not included in the analysis. Also not included was the period of medical treatment from symptom onset to transplantation. Another issue of importance is the study’s execution as a single-center study of only modest size. We hope for large-scale studies that will confirm our findings. Our study stands as the first exploration into the actual psychological state (and thus the quality of life) of haplo-HSCT patients. During the years 2013 through 2016, considered the “dawn” of haplo-HSCT, Tokyo Metropolitan Komagome Hospital led the way in implementing haplo-HSCT in Japan. The number of patients requiring HSCT is expected to increase in the coming years, and we believe our findings will, at the very least, inform future clinical practice in terms of interventions. CONCLUSION
Attention should be paid to the matter of psychological distress in patients with leukemia who will be treated with HSCT, even
HLA-HAPLOIDENTICAL HEMATOPOIETIC STEM CELL
haplo-HSCT. Such patients need psychological support not only immediately prior to the transplantation procedure but also during other parts of the decision-making process. ACKNOWLEDGEMENTS We thank Professor Tina Tajima of St. Marianna University School of Medicine for comments that greatly improved the manuscript.
REFERENCES [1] Baker F, Marcellus D, Zabora J, Polland A, Jodrey D. Psychological distress among adult patients being evaluated for bone marrow transplantation. Psychosomatics 1997;38:10e9. [2] Sasaki T, Akaho R, Sakamaki H, Akiyama H, Yoshino M, Hagiya K, et al. Mental disturbances during isolation in bone marrow transplant patients with leukemia. Bone Marrow Transplant 2000;25:315e8. [3] Baliousis M, Rennoldson M, Snowden JA. Psychological intervention for distress in adults undergoing haematopoietic stem cell transplantation: a systematic review with meta-analysis. Psychooncology 2016;25:400e11. [4] Warchala A, Wojtyna E, Krysta K. Mental state and its psychophysical conditions in patients with acute leukemia treated with bone marrow transplantation. Psychiatr Danub 2015;27: S415e22. [5] The Japanese Data Center for Hematopoietic Cell Transplantation. Activities and outcomes of hematopoietic cell
1993 transplantation in Japan. http://www.jdchct.or.jp/data/slide/2017/. [Accessed 18 December 2018]. [6] Lennard AL, Jackson GH. Stem cell transplantation. BMJ 2000;321:433e7. [7] Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor vs identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood 2012;119:3908e16. [8] O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2002;8:377e86. [9] Ogawa H, Ikegame K, Yoshihara S, Kawakami M, Fujioka T, Masuda T, et al. Unmanipulated HLA 2-3 antigenmismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. Biol Blood Marrow Transplant 2006;12:1073e84. [10] 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;106:2912e9. [11] Elsawy M, Sorror ML. Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2016;51:1283e300. [12] Raj M, Choi SW, Platt J. A qualitative exploration of the informed consent process in hematopoietic cell transplantation clinical research and opportunities for improvement. Bone Marrow Transplant 2017;52:292e8.
ABSTRACT Background. The psychological distress experienced by patients scheduled for hematopoietic stem cell transplantation (HSCT) is of clinical concern. However, distress experienced by patients scheduled for HLA-haploidentical HSCT vs that of patients scheduled for other types of matched HSCT is unknown. We conducted a retrospective study to clarify whether the type of HSCT influences the appearance of psychological distress in patients anticipating HSCT. Methods. One hundred fifty-seven patients who had undergone any of 4 types of HSCT at Tokyo Metropolitan Komagome Hospital between October 2013 and September 2016 and had completed the Profile of Mood States (POMS) questionnaire within 2 weeks before the procedure were included. We computed T-scores for the tension-anxiety (TA) and depression (D) subscales, took scores 60 to represent mood disturbance of clinical concern, and examined scores and other clinical variables in relation to each procedure. Results. Twenty-two (14.0%) patients had a POMS-TA score 60, and 26 (16.6%) had a POMS-D score 60. The numbers of POMS-TA and POMS-D scores 60 did not differ significantly with respect to age, sex, leukemia type, number of previous transplants, disease status, comorbidity index, or transplant type. A multivariate logistic regression analysis confirmed the absence of an influence of the type of HSCT on the incidence of POMSTA or POMS-D scores 60. Conclusion. Attention should be paid to the matter of psychological distress in patients with leukemia who will be treated by HSCT, even HLA-haploidentical HSCT. Such patients need psychological support, especially during the waiting period immediately prior to the transplantation procedure.
H
EMATOPOIETIC stem cell transplantation (HSCT) is potentially curative in patients with leukemia. Until the 1990s, the potential for anxiety and depression in patients undergoing HSCT was a matter of great concern [1,2], especially because it was generally understood that possible complications such as infections and graft-versus-host disease (GVHD) were not well controlled. Since the early 2000s, advances in transplantation medicine, including infection control, have reduced patients’ physical distress, and various interventions have been introduced to alleviate
0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.03.029
1990
the psychological distress associated with HSCT [3]. Nevertheless, psychological distress remains a matter of concern for patients scheduled for HSCT [4].
*Address correspondence to Rie Akaho, MD, PhD, Department of Psychiatry, Tokyo Women’s Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: akaho.rie@ twmu.ac.jp ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 1990e1993 (2019)
HLA-HAPLOIDENTICAL HEMATOPOIETIC STEM CELL
Currently, 4 types of HSCT are practiced. The first is human leukocyte antigen (HLA)-matched related donor (MRD) HSCT. An MRD is the most suitable donor for HSCT, but an MRD exists in only about 30% of cases [5,6]. The second is HLA-matched unrelated donor (MUD) HSCT, which means that HLA-matched bone marrow is obtained from a bone marrow bank [7]. The third is umbilical cord blood HSCT (CBT), which means that cord blood is obtained for transplantation, and the fourth is HLA-haploidentical HSCT (haplo-HSCT), which means that the transplant material is obtained from a halfmatched donor. This method is especially useful when finding a suitable donor becomes a long-drawn-out procedure. Haplo-HSCT has been problematic in terms of both GVHD and rejection, the risks of which are high in comparison to those associated with matched transplantation. Progress in transplantation medical care, however, led to widespread use of haplo-HSCT, beginning around 2013 [5,8,9]. Haplo-HSCT is considered the treatment of choice for patients for whom matched donor transplantation is not possible. The physical distress of these patients in comparison to that of matched donor recipients is well known, but there is no report regarding the psychological distress experienced by haplo-HSCT recipients vs that of matched transplant recipients. We conducted the retrospective comparative study described herein to clarify whether the type of HSCT influences the appearance of psychological distress in patients expecting to undergo HSCT. The study was conducted at Tokyo Metropolitan Komagome Hospital, which pioneered research on haplo-HSCT in Japan. MATERIALS AND METHODS Study Patients We included in the study all 157 patients who underwent HSCT for leukemia at Tokyo Metropolitan Komagome Hospital between October 1, 2013 and September 30, 2016. The patients were identified from departmental records, and the study was approved by the Ethics Committee of Tokyo Metropolitan Komagome Hospital (approval no. 2174).
Study Variables We obtained the following data from patients’ clinical records: age, sex, leukemia type, number of previous transplants, disease status, hematopoietic cell transplantationespecific comorbidity index (HCT-CI), and transplant type. Age was categorized as 10 to 39 years, 40 to 59 years, or 60 years or more. The disease itself was classified as acute myelogenous (myeloid) leukemia or acute lymphoblastic (lymphoid) leukemia. Disease status was classified as first or second complete remission (for which the post-transplant prognosis is generally good) or other (ie, primary induction failure, partial remission, or third complete remission [for which the post-transplant prognosis is generally poor]). HCT-CIs range from 0 to 5 and are used to classify comorbidities that might affect a patient’s risk of death. When there are no comorbidities, the HCT-CI is 0; when the HCT-CI is 3 or more, the patient’s risk of death from a comorbidity is quite high [10].
1991
Assessment of Psychological Distress Approximately 2 weeks before performance of the HSCT procedure, each patient had been asked, as a matter of routine, to complete the Profile of Mood States (POMS) questionnaire, which is a validated self-report psychological inventory used to assess transient feelings and mood states. POMS, widely used in Western countries and translated into Japanese, measures 6 mood states: tension-anxiety, depressiondejection, anger-hostility, vigor, fatigue, and confusion. Thus, in addition to the clinical variables noted, we obtained patients’ POMS scores, focusing on 2 subscales: the tension-anxiety (POMS-TA) subscale, a 9-item subscale with scores ranging from 0 to 36, and the depression-dejection (POMS-D) subscale, a 15-item subscale with scores ranging from 0 to 60. We obtained scores from the patients’ records, and we computed individual T scores for each of the 2 subscales, with a T score of 60 (SD 1) or more taken to represent a greater-than-expected mood disturbance.
Statistical Analysis Age, sex, leukemia type, number of previous transplants, disease status, HCT-CI, and HSCT type were examined in relation to POMS-TA scores (<60 vs 60) and in relation to POMS-D scores (<60 vs 60), and differences were analyzed using the c2 test. A logistic regression analysis was then performed to analyze the influence of HSCT type on POMS-TA and POMS-D scores, with adjustment made for age, sex, leukemia type, number of previous transplants, and HCT-CI. All statistical analyses were performed with SPSS version 20, and P < .05 was accepted as statistically significant.
RESULTS Patient Characteristics
The characteristics of the 157 study patients are shown in Table 1. Patients ranged in age from 18 to 70 years, with a mean age of 47.9 13.5 years. The male:female ratio was 105:52. All 4 types of transplant were performed among this group of patients: HLA-MRD HSCT in 26 patients, HLAMUD HSCT in 76, CBT in 19, and haplo-HSCT in 36. Psychological Distress
Thirty (19.1%) of the 157 patients reported psychological distress at or above the threshold level, with 22 (14.0%) having a POMS-TA score 60, 26 (16.6%) having a POMSD score 60, and 18 (11.5%) having both POMS-TA and POMS-D scores 60. Relation Between Psychological Distress and HSCT Type
The numbers of POMS-TA and POMS-D scores 60 did not differ significantly in relation to age, sex, leukemia type, number of previous transplants, disease status, HCT-CI, or transplant type. Multivariate logistic regression analysis confirmed the absence of an influence of the type of HSCT on the occurrence of POMS-TA scores 60, with odds ratios for such scores related to MRD, MUD, and CBT (vs haploHSCT) of 1.664, 1.746, and 1.92, respectively (Table 2). Multivariate logistic regression analysis also confirmed the absence of an influence of the type of HSCT on POMS-D scores 60 (with odds ratios of 1.11, 0.725, and 0.739, respectively) (Table 2).
1992
AKAHO, OTSU, IGARASHI ET AL
Table 1. Clinical Characteristics of the Patients Included in the Study (N [ 157) Variable
No. of Patients
Age Range (y) 10e39 40e59 60 Sex Male Female Leukemia Type AML ALL/LBL Disease Status First or second CR Other HCT-CI 0 1e2 3 No. of Previous Transplants 0 1 2 Type of HSCT Haplo Matched related Matched unrelated CBT
39 77 41 105 52 101 56 98 59 77 47 33 142 14 1 36 26 76 19
Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; CR, complete remission; CBT, umbilical cord blood HSCT; Haplo, HLAhaploidentical HSCT; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HSCT, hematopoietic stem cell transplantation; LBL, lymphoblastic lymphoma; Matched related, HLA-matched related HSCT; Matched unrelated, HLA-matched unrelated HSCT; Other, primary induction failure, partial remission, or third complete remission.
DISCUSSION
In this study, we focused on the potential for psychological distress experienced by patients expecting to undergo haploHSCT, a relatively new type of HSCT. We are particularly Table 2. Relations Between Presence of Psychological Distress (Shown by POMS-TA and POMS-D) and Type of HSCT POMS-TA 60 Haplo Matched related Matched unrelated CBT POMS-D 60 Haplo Matched related Matched unrelated CBT
OR*
95% CI
P Value
(reference) 1.664 1.746 1.92
0.320e8.654 0.428e7.116 0.323e11.395
.545 .437 .473
(reference) 1.11 .725 .739
0.284e4.338 0.220e2.386 0.149e3.677
.881 .596 .712
Abbreviations: CBT, umbilical cord blood HSCT; CI, confidence interval; Haplo, haploidentical HSCT; HCT-CI, hematopoietic cell transplantationspecific comorbidity index; HSCT, hematopoietic stem cell transplantation; Matched related, HLA-matched related HSCT; Matched unrelated, HLAmatched unrelated HSCT; OR, odds ratio; POMS-D, Profile of Mood Statesdepression-dejection subscale; POMS-TA, Profile of Mood States-tensionanxiety subscale. *Adjusted for age, sex, leukemia type, number of previous transplants, and HCT-CI.
interested in any psychological distress associated with haploHSCT compared with that associated with MRD, MUD, and CBT because haplo-HSCT is used especially for patients for whom donor coordination or the patient’s condition make other options unrealistic. We found patients’ psychological stress levels to be similar, regardless of the type of HSCT planned. We evaluated our study results from 2 standpoints. First, we asked ourselves how well the patients understood and recognized the difference between haplo-HSCT and other transplant methods. For informed consent before transplantation, various support systems have been advanced to help patients understand the information provided and make decisions [11,12]. At Tokyo Metropolitan Komagome Hospital, information is provided in booklet form. The important information is explained in simple terms and the booklets are easy to read. For patients who will undergo haplo-HSCT, we use the same booklet we use for other patients who will undergo HLA-matched transplantation and explain the likelihood of GVHD and the need for highdose immunosuppressive agents. The information is provided in such a way as to alleviate patients’ sense of fear. Second, we asked ourselves about the timing of the psychological distress. Patients scheduled to undergo haplo-HSCT may have experienced stress for a fairly long period of time preceding the decision to perform haplo-HSCT. These patients might have searched for and not found an MRD or MUD and thus experienced the stress of uncertainty during the decision-making period. The POMS questionnaire was administered within a short 2-week period before transplantation (and after the type of transplant had been decided), so any psychological distress experienced by patients early during the decision-making process would not have been detected. We can assume, however, that the psychological state of patients already scheduled for haplo-HSCT, despite the known difficulties, is similar to that of patients scheduled for other types of transplant. We recognize that our study results should be interpreted in light of the study limitations, which include that fact that socioeconomic factors that might have influenced patients’ distress levels, such as the presence vs absence of family support and employment, were not included in the analysis. Also not included was the period of medical treatment from symptom onset to transplantation. Another issue of importance is the study’s execution as a single-center study of only modest size. We hope for large-scale studies that will confirm our findings. Our study stands as the first exploration into the actual psychological state (and thus the quality of life) of haplo-HSCT patients. During the years 2013 through 2016, considered the “dawn” of haplo-HSCT, Tokyo Metropolitan Komagome Hospital led the way in implementing haplo-HSCT in Japan. The number of patients requiring HSCT is expected to increase in the coming years, and we believe our findings will, at the very least, inform future clinical practice in terms of interventions. CONCLUSION
Attention should be paid to the matter of psychological distress in patients with leukemia who will be treated with HSCT, even
HLA-HAPLOIDENTICAL HEMATOPOIETIC STEM CELL
haplo-HSCT. Such patients need psychological support not only immediately prior to the transplantation procedure but also during other parts of the decision-making process. ACKNOWLEDGEMENTS We thank Professor Tina Tajima of St. Marianna University School of Medicine for comments that greatly improved the manuscript.
REFERENCES [1] Baker F, Marcellus D, Zabora J, Polland A, Jodrey D. Psychological distress among adult patients being evaluated for bone marrow transplantation. Psychosomatics 1997;38:10e9. [2] Sasaki T, Akaho R, Sakamaki H, Akiyama H, Yoshino M, Hagiya K, et al. Mental disturbances during isolation in bone marrow transplant patients with leukemia. Bone Marrow Transplant 2000;25:315e8. [3] Baliousis M, Rennoldson M, Snowden JA. Psychological intervention for distress in adults undergoing haematopoietic stem cell transplantation: a systematic review with meta-analysis. Psychooncology 2016;25:400e11. [4] Warchala A, Wojtyna E, Krysta K. Mental state and its psychophysical conditions in patients with acute leukemia treated with bone marrow transplantation. Psychiatr Danub 2015;27: S415e22. [5] The Japanese Data Center for Hematopoietic Cell Transplantation. Activities and outcomes of hematopoietic cell
1993 transplantation in Japan. http://www.jdchct.or.jp/data/slide/2017/. [Accessed 18 December 2018]. [6] Lennard AL, Jackson GH. Stem cell transplantation. BMJ 2000;321:433e7. [7] Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor vs identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood 2012;119:3908e16. [8] O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2002;8:377e86. [9] Ogawa H, Ikegame K, Yoshihara S, Kawakami M, Fujioka T, Masuda T, et al. Unmanipulated HLA 2-3 antigenmismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. Biol Blood Marrow Transplant 2006;12:1073e84. [10] 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;106:2912e9. [11] Elsawy M, Sorror ML. Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2016;51:1283e300. [12] Raj M, Choi SW, Platt J. A qualitative exploration of the informed consent process in hematopoietic cell transplantation clinical research and opportunities for improvement. Bone Marrow Transplant 2017;52:292e8.