Quality of life of patients with graft-versus-host disease (GvHD) post-hematopoietic stem cell transplantation / Calidad de Vida de Pacientes Post Trasplante de Células Madre Hematopoyéticas con Enfermedad del Injerto Contra Huésped / Qualidade de vida de pacientes pós-transplante de células-tronco hematopoéticas com doença do enxerto-hospedeiro

Abstract OBJECTIVE Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD) is predictive of worse results. METHOD An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT The mean age was 37 years, 52.78% were female, and 61.11% were diagnosed with leukemia. Quality of life scores showed a significant impact between pre-transplantation and pre-hospital discharge, and also within the 100 days post-transplantation. The statistical analysis between the scores for the groups with and without GvHD showed a significant difference between the presence of the complication and worse results. CONCLUSION Quality of life is altered as a result of hematopoietic stem cells transplantation, especially in patients who have graft-versus-host disease.

Resumen OBJETIVO Evaluar la calidad de vida de paciente adultos con cáncer hematológico los 100 días tras el trasplante de células madre hematopoyéticas y verificar si la variable enfermedad del injerto contra huésped es predictiva de peores resultados. MÉTODO Estudio observacional, correlacional y cuantitativo, con 36 participantes adultos, diagnosticados con cáncer hematológico que se sometieron al trasplante de células madre hematopoyéticas de septiembre de 2013 a junio de 2015. RESULTADO El promedio de edad fue 37 años, el 52,78% eran del sexo femenino y el 61,11% con diagnóstico de leucemia. Los puntajes de calidad de vida demostraron impacto significativo entre el pre trasplante y la pre alta hospitalaria y entre los 100 días post trasplante. El análisis estadístico entre los puntajes de los grupos con y sin enfermedad del injerto contra huésped evidenció significación entre la presencia de esa complicación y peores resultados. CONCLUSIÓN La calidad de vida se modifica como consecuencia del trasplante de células madre hematopoyéticas, en especial en los pacientes que presentan enfermedad del injerto contra huésped.

Resumo OBJETIVO Avaliar a qualidade de vida de pacientes adultos com câncer hematológico nos 100 dias do transplante de células-tronco hematopoéticas e verificar se a variável doença do enxerto contra o hospedeiro é preditiva de piores resultados. MÉTODO Estudo observacional, correlacional e quantitativo, com 36 participantes adultos, diagnosticados com câncer hematológico que se submeteram ao transplante de células-tronco hematopoéticas de setembro de 2013 a junho de 2015. RESULTADO A média de idade foi 37 anos, 52,78% eram do sexo feminino, e 61,11% com diagnóstico de leucemia. Os escores de qualidade de vida demonstraram impacto significativo entre o pré-transplante e a pré-alta hospitalar e entre os 100 dias pós-transplante. A análise estatística entre os escores dos grupos com e sem doença do enxerto contra o hospedeiro evidenciou significância entre a presença desta complicação e piores resultados. CONCLUSÃO A qualidade de vida é alterada em decorrência do transplante de células-tronco hematopoéticas, em especial nos pacientes que apresentam doença do enxerto contra o hospedeiro.

Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations.

The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality.

High-Resolution Match Rate of 7/8 and 9/10 or Better for the Be The Match Unrelated Donor Registry.

Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy.

Risk factors for the development of ocular graft-versus-host disease (GVHD) dry eye syndrome in patients with chronic GVHD.

BACKGROUND: To investigate the factors associated with the development of ocular graft-versus-host disease (oGVHD) dry eye syndrome (DES) in patients with chronic GVHD (cGVHD) after receiving allogenic haematopoietic stem cell transplantation (AHSCT) METHODS: A retrospective chart review of patients receiving AHSCT between 1998 and 2013 at the Bone Marrow Transplant Unit of the British Columbia Cancer Agency was carried out. Demographic and clinical data from both donors and recipients were obtained. The diagnostic criteria for the development of oGVHD DES from the National Institutes of Health were used to identify patients with the disease. Descriptive and inferential statistics were carried out. RESULTS: A total of 146 patients with a median follow-up time of 24.0 months (range 11.3-249.7 months) were included in this study. Sixty-six (45.2%) patients were women. Seventy-seven (52.7%) patients had oGVHD DES. The median age of patients was 57 years (range 25-71 years). Compared with other ethnicities, Caucasian patients were less likely to develop oGVHD DES, with an OR of 0.29 (p=0.01). Patients who received a transplant from Epstein-Barr-positive donors had a higher prevalence of oGVHD DES (OR=4.39, p=0.01). This was also found in patients with the following systemic involvement of cGVHD: grade 1-3 cGVHD skin involvement (OR=1.57, p=0.01), oral involvement (OR=2.51, p=0.01) and liver involvement (p=0.04). Patients with grade 2-3 overall cGVHD were also more susceptible to oGVHD DES (OR=2.72, p<0.001). CONCLUSIONS: This study identified risk factors associated with a higher prevalence of oGVHD DES in post-AHSCT patients with cGVHD.

Racial differences in allogeneic hematopoietic cell transplantation outcomes among African Americans and whites.

The impact of race on outcome has been identified in a number of cancers, with African Americans having poorer survival compared with whites. We conducted a study to investigate the association of race with allogeneic hematopoietic cell transplant (HCT) outcomes. We identified 789 patients (58 African Americans and 731 whites) who underwent allogeneic HCT for hematologic disorders. There were no significant differences between African Americans and white patients in gender, performance status or comorbidity score. However, African Americans were younger than whites (median 40 years versus 47 years, P=0.003) and were more likely to be in remission at HCT (74% versus 57%, P=0.011), to have an HLA-mismatched donor (36% versus 14%, P<0.001), to have positive donor or recipient CMV serostatus (90% versus 69%, P<0.001) and to have received a cord blood transplant (21% versus 6%, P<0.001). In univariate analysis, African Americans had worse overall survival (OS) (HR 1.41, P=0.026) compared with whites, with no significant differences in acute or chronic GvHD, non-CMV infection or relapse. However, after adjusting for several transplant and disease-related factors in multivariate analysis, the OS difference between African Americans and whites became nonsignificant (HR 1.27, P=0.18). These results suggest that race in and of itself does not lead to worse survival post HCT.

Graft-versus-host disease and survival after cord blood transplantation for acute leukemia: a comparison of Japanese versus White populations.

An earlier report identified higher risks of acute and chronic graft-versus-host disease (GVHD) in White children compared with the Japanese after HLA-matched sibling transplantations. The current analysis explored whether racial differences are associated with GVHD risks after unrelated umbilical cord blood transplantation. Included are patients of Japanese descent (n = 257) and Whites (n = 260; 168 of 260 received antithymocyte globulin [ATG]). Transplants were performed in the United States or Japan between 2000 and 2009; patients were aged 16 years or younger, had acute leukemia, were in complete remission, and received a myeloablative conditioning regimen. The median ages of the Japanese and Whites who received ATG were younger at 5 years compared with 8 years for Whites who did not receive ATG. In all groups most transplants were mismatched at 1 or 2 HLA loci. Multivariate analysis found no differences in risks of acute GVHD between the Japanese and Whites. However, chronic GVHD was higher in Whites who did not receive ATG compared with the Japanese (hazard ratio, 2.16; P < .001), and treatment-related mortality was higher in Whites who received ATG compared with the Japanese (relative risk, 1.81; P = .01). Nevertheless, there were no significant differences in overall survival between the 3 groups.

Importance of donor ethnicity/race matching in unrelated adult and cord blood allogeneic hematopoietic cell transplant.

Donor race matching (both recipient and donor belonging to the same race) might be a factor in outcomes of donor allogeneic hematopoietic cell transplant (alloHCT). A total of 858 patients who underwent umbilical cord blood (UCB) (475 patients: 202 double UCB and 273 single UCB) or unrelated donor (URD) (383 patients) alloHCT between January 1995 and December 2010 were studied. Most patients were Caucasian (87%), followed by Asians (4%), African Americans (3%), Hispanics (3%), mixed race (3%) and American Indians (< 1%). Caucasians constituted 88% of the donor grafts; Caucasians were the most common race of the donor grafts among all races except for Asians. As a result, Caucasians were much more likely to have a race-matched donor than ethnic minorities (91% vs. 33%, p < 0.01). Donor race matching did not affect non-relapse mortality, relapse, acute or chronic graft-versus-host disease or overall survival. Acknowledging the limitations of this study (mainly, self-reported race information and small number of ethnic minorities), at present there are no data supporting that donor race should be considered a factor in donor selection.

Significance of ethnicity in the risk of acute graft-versus-host disease and leukemia relapse after unrelated donor hematopoietic stem cell transplantation.

The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient-donor pairs from the International Histocompatibility Working Group in HCT met the following 3 criteria: (1) HLA-A, -B, -C, -DRB1, and -DQB1 allele matched donor, (2) diagnosis of leukemia, and (3) non-T cell depleted GVHD prophylaxis. Posttransplantation risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, white, African American, Hispanic, and Native American patients that underwent transplantation from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II to IV and 15.3% grades III to IV; non-Japanese Asian patients: 42.1% grades II to IV and 15.7% grades III to IV) compared with white patients (56.5% grades II to IV and 22.6% grades III to IV) (P < .001). The hazard ratio of acute GVHD for white patients was significantly higher than for Japanese patients. Unexpectedly, the hazard ratio of leukemia relapse in white patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background.

Transforming growth factor-beta1 codon 10 polymorphism is associated with acute GVHD after allogenic BMT in Iranian population.

BACKGROUND: Certain cytokine genotypes are associated with acute graft versus host disease (aGVHD) after bone marrow transplantation (BMT). The present study aimed to determine existing association between TGF-beta1 codon 10 polymorphism and aGVHD after HLA-identical sibling BMT in the Iranian population. MATERIAL/METHODS: In a retrospective case-control study, 168 subjects including 84 Iranian HLA-identical sibling BMT donor/recipient pairs were recruited. All of the patients were affected by hematological malignancies (AML=39, ALL=23 and CML=22). PCR-SSP method was performed to determine TGF-beta1 codon 10 T/C polymorphism genotypes. RESULTS: The frequency of TGF-beta1 codon 10 TT, TC and CC genotypes among all subjects were 26.8%, 33.3% and 39.9% respectively. Recipients with the T allele developed aGVHD significantly less than those without the T allele (odds ratio =0.334, P=0.026). CONCLUSIONS: Genetic background of TGF-beta1 may be involved as a protective factor in the development of aGVHD in HLA-matched sibling BMT in Iranian population. Moreover, this finding may indicate that the genetic markers in Iranians are, at least to some extent, linked to distinct genetic event from Japanese.

Outcome of ethnic minorities with acute or chronic leukemia treated with hematopoietic stem-cell transplantation in the United States.

PURPOSE: We previously reported a higher risk of mortality among Hispanics after allogeneic hematopoietic stem-cell transplantation (HSCT). However, it is not known how specific post-transplantation events (acute or chronic graft-versus-host disease [GVHD], treatment-related mortality [TRM], and relapse) may explain mortality differences. The purpose of this study was to examine the relationship between ethnicity and post-transplantation events and determine their net effect on survival. PATIENTS AND METHODS: We identified 3,028 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myeloid leukemia reported to the International Bone Marrow Transplant Registry between 1990 and 2000 who received an HLA-identical sibling HSCT after a myeloablative conditioning regimen in the United States. There were 2,418 white patients (80%) and 610 ethnic minority patients (20%), of whom 251 were black (8%), 122 were Asian (4%), and 237 were Hispanic (8%). Cox proportional hazards regression was used to compare outcomes between whites and ethnic minorities while adjusting for other significant clinical factors. RESULTS: No statistically significant differences in the risk of acute or chronic GVHD, TRM, or relapse were found between whites and any ethnic minority group. However, Hispanics had higher risks of treatment failure (death or relapse; relative risk [RR] = 1.30; 95% CI, 1.08 to 1.54; P = .004) and overall mortality (RR = 1.23; 95% CI, 1.03 to 1.47; P = .02). CONCLUSION: The higher risks of treatment failure and mortality among Hispanics may be the net result of modest but not statistically significant increases in both relapse and TRM and cannot be accounted for by any single transplantation-related complication. Further studies should examine the role of social, economic, and cultural factors.

Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients.

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.

An ethnic role for chronic, but not acute, graft-versus-host disease after HLA-identical sibling stem cell transplantation.

Among 424 HLA identical siblings undergoing stem cell transplantation, 364 were Scandinavians and 60 represented other ethnic groups. The cumulative probabilities of acute graft-versus-host disease grades II-IV were similar in both groups, 17% in Scandinavians and 12% in the others, p = 0.4. In a multivariate analysis, less effective immune suppression with cyclosporine or methotrexate alone (p = 0.001), recipient seropositive for three to four herpes viruses (p = 0.004), CMV-seropositive recipient (p = 0.05) and early engraftment (before day 15) (p = 0.05) were independent risk-factors for acute GVHD grades II-IV. The cumulative probabilities of chronic GVHD were 47% and 68% in the two ethnic populations, respectively (p = 0.004). In multivariate analysis, higher patient age (p < 0.001), non-Scandinavian population (p < 0.001) and immunised female donor to male recipient (p = 0.03) were independent risk factors for chronic GVHD. The higher incidence of chronic GVHD could not be explained by differences in HLA antigen frequencies. The cumulative probabilities of relapse were 37% in the both groups. This suggests that the Scandinavian population is more homogeneous with regard to minor histocompatibility antigens important for chronic, but not acute GVHD.

Graft-versus-host disease. Possible higher risk for African American patients.

BACKGROUND: Race is not generally recognized as a factor in the severity or incidence of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The impression that African American patients had more frequent and severe GVHD prompted this retrospective survey. METHODS: The records of 75 consecutive patients treated with a human leukocyte antigen-identical sibling bone marrow transplant from 1985 to 1993 were reviewed. GVHD prophylaxis uniformly employed cyclosporine and steroids. Treatment of GVHD included cyclosporine and high dose steroids in all cases. Antithymocyte globulin and other immunosuppressants were used in severe cases. RESULTS: Of 75 patients, 56 (75%) were white, 11 (15%) were listed as "Hispanic", 7 (9%) were African Americans, and 1 was of Far-Eastern origin. Four of the African American patients had chronic myelogenous leukemia and 2 had acute leukemia, whereas 21 of the other 68 patients (31%) had chronic myelogenous leukemia, 31 (46%) had acute leukemia, and the remainder (33%) had miscellaneous hematologic malignancies. Transplants from a female donor to a male recipient were performed in 2 of 7 African Americans and 19 of 68 patients (28%) of other origins. Five of the 6 evaluable African American patients (83%; 95% confidence interval, 36-100%) had Grade 4 GVHD, as opposed to 5 of 61 patients of other racial origins (8%; 95% confidence interval, 3-18%). All African American patients died within 90 days of transplant. CONCLUSIONS: Patients of African American origin possibly have a greater risk of GVHD.

Incidence of graft-versus-host disease in Hong Kong Chinese and its influence on survival after bone marrow transplantation from HLA-identical siblings.

Graft-versus-host disease (GVHD) is an important complication of allogeneic bone marrow transplantation (BMT). To assess its influence on transplant outcome, we studied 90 Chinese patients with hematologic disorders with BMT from HLA-identical siblings. GVHD prophylaxis consisted of a combination of methotrexate (MTX) and cyclosporine A (CsA). The incidence of grade II-IV acute GVHD was 29% (95% CI 19-38%). The incidence of limited and extensive chronic GVHD was 30% (95% CI 20-40%). For patients transplanted for early hematologic malignancy (n = 40), those with GVHD (acute and/or chronic) had lower relapse rate (17% (95% CI 0-36%) vs. 54% (95% CI 26-82%), P = 0.043). They had higher transplant-related mortality (12% (95% CI 0-28%) vs. 6% (95% CI 0-18%), P = 0.715) and event-free survival (EFS) (73% (95% CI 53-93%) vs. 43% (95% CI 17-69%), P = 0.104) that had not reached statistical significance. For patients transplanted for advanced hematologic malignancy (n = 37), those with GVHD also had lower relapse rate (5% (95% CI 0-15%) vs. 72% (95% CI 50-94%), P = 0.002) and higher transplant-related mortality (50% (95% CI 27-73%) vs. 8% (95% CI 0-24%), P = 0.006) than those without any GVHD. They had higher EFS (47% (95% CI 24-70%) vs. 26% (95% CI 5-47%), P = 0.609) that had not reached statistical significance. Therefore, the incidence of acute and chronic GVHD in Chinese was similar to that of their Caucasian counterparts using MTX and CsA for GVHD prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of transfusion-associated graft-versus-host disease.

Recent investigations have revealed that transfusion-associated graft-versus-host disease (TA-GVHD) occurs in patients whose immune system is immature or impaired, but also in immunocompetents. The mechanism of TA-GVHD in immunocompromised patients is that donor's viable lymphocytes can not be rejected by the recipient because of defects in cellular immunity. While, even in immunocompetent patients, TA-GVHD may occur when an HLA-heterozygous recipient receives blood from a donor who is homozygous for one of the patient's haplotypes. Engraftment of donor's lymphocytes may be established without rejection, as the donor's homozygous lymphocytes are identical with one of the patient's haplotypes in HLA. Our calculations show that the Japanese have a greatest risk of TA-GVHD than other populations among relatives and unrelated donors.