INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and nonmalignant diseases. Improved long-term survival after HSCT translates into coming across secondary neoplasms. Contributory factors include primary disease, male sex, young age, prior therapies, conditioning regimens. The secondary neoplasms are particularly solid tumors, as well as lymphoproliferative disorders. Chronic graft-versus-host disease (GvHD) and immunosupressive therapy have also been reported to contribute to neoplasia risk.

OBJECTIVE: The purpose of this study was to evaluate the frequency and distribution of the posttransplant secondary neoplasms in our center, to determine the possible contributory factors and relative effect of GvHD.

METHODS: From 457 patients who received a HSCT between 1994-2014 clinical records of 312 patients were available to review retrospectively. 21 patients diagnosed with a secondary neoplasia in the posttransplant period are included in the study. Age, sex, primary diagnosis and treatment, time of HSCT, GvHD and immunosupressive treatments, localisation of neoplasms and outcomes were reported.

RESULTS: Twenty-one cases of secondary neoplasms were observed (%6,7). The median age at diagnosis and transplantation were 44 and 47, respectively. The median follow-up time was 122 months (32-304). The most common primary diagnosis was Hodgkin's disease (HD). The most commonly used pretransplant conditioning regimen was BEAM. There were no cases of acute GvHD, chronic GvHD was observed in 3 cases. The most common secondary neoplasm was skin cancer followed by urogenital system cancers. The secondary malignancies seen in cases with chronic GvHD are concordant with GvHD sites. Three patients had benign neoplasms comprising fibroadenoma, mol hydatiforme and hibernoma; 2 patients developed preinvasive lesions of vulva (VIN 3) and oral cavity (squamous papilloma). For 20 patients the median time interval between the date of HSCT and diagnosis of a secondary neoplasia is 62 months (5-118); data is missing for 1 case. Two deaths were observed, 1 due to disease progression, 1 due to secondary colorectal malignancy. %90,4 of the study group are alive and in remission. Details are listed in Table 1 and 2.

CONCLUSION: Patients undergoing HSCT have an increased risk of secondary cancers later in life. Known risk factors are primary disease, age at transplantation, pretransplant therapies, pretransplant conditioning regimens like total body irradiation, chronic GvHD and immunosuppressive therapies. Our study group is small to comment on these risk factors. Coherent with the literature skin cancer was the most common secondary cancer in our cohort as well. Interestingly we observed a trend towards increased urogenital cancers in comparison to reported data. This finding can be incidental because of the small number of study population or needs to be clarified yet. The increased risk of secondary neoplasms over time after transplantation and the greater risk among younger patients indicate the need for lifelong surveillance.

Table 1

Characteristics of patients with secondary neoplasms after HSCT

Characteristicn (%)
Sex   
 Female 10 (%47) 
 Male 11 (%53) 
Primary diagnosis   
 Acute myeloid leukemia 1 (%4,7) 
 Acute lymphoblastic leukemia 3 (%14,3) 
 Chronic myelogeneous leukemia 3 (%14,3) 
 Multiple Myeloma 5 (%23,8) 
 Hodgkin’s disease 6 (%28,6) 
 Non-Hodgkin’s lymphoma 3 (%14,3) 
Prior therapy   
 Chemotherapy 9 (%42,7) 
 Chemoimmunotherapy 3 (%14,3) 
 Chemoradiotherapy 5 (%23,7) 
 Combination treatment* 3 (%14,3) 
Type of HSCT   
 Allogeneic 5 (%23,8) 
 Related 
 Unrelated 
 Autologous 15(%71,5) 
 Both 1(%4,7) 
Conditioning regimens   
 TBI+Cy 3 (%14,3) 
 BEAM 8 (% 38,1) 
 MEL 6 (% 28,6) 
 BU+Cy 2 (% 9,5) 
 Unknown 2 (%9,5) 
Acute GvHD  
Chronic GvHD 3 (%14,3)  
 Skin 
 Oral cavity 
 Eye 
 Pulmonary 
 Hepatic 
Acute GvHD prophylaxis 7 (%33,3)  
  CsA 
 MTX+CsA 
Chronic GvHD treatment 3 (14,3)  
 Steroid+CsA 
 CsA 
Characteristicn (%)
Sex   
 Female 10 (%47) 
 Male 11 (%53) 
Primary diagnosis   
 Acute myeloid leukemia 1 (%4,7) 
 Acute lymphoblastic leukemia 3 (%14,3) 
 Chronic myelogeneous leukemia 3 (%14,3) 
 Multiple Myeloma 5 (%23,8) 
 Hodgkin’s disease 6 (%28,6) 
 Non-Hodgkin’s lymphoma 3 (%14,3) 
Prior therapy   
 Chemotherapy 9 (%42,7) 
 Chemoimmunotherapy 3 (%14,3) 
 Chemoradiotherapy 5 (%23,7) 
 Combination treatment* 3 (%14,3) 
Type of HSCT   
 Allogeneic 5 (%23,8) 
 Related 
 Unrelated 
 Autologous 15(%71,5) 
 Both 1(%4,7) 
Conditioning regimens   
 TBI+Cy 3 (%14,3) 
 BEAM 8 (% 38,1) 
 MEL 6 (% 28,6) 
 BU+Cy 2 (% 9,5) 
 Unknown 2 (%9,5) 
Acute GvHD  
Chronic GvHD 3 (%14,3)  
 Skin 
 Oral cavity 
 Eye 
 Pulmonary 
 Hepatic 
Acute GvHD prophylaxis 7 (%33,3)  
  CsA 
 MTX+CsA 
Chronic GvHD treatment 3 (14,3)  
 Steroid+CsA 
 CsA 
Table 2

Characteristics and risk factors of patients who had secondary malignancy undergoing HSCT

BreastSkinGISUrogenitalLungLymphoma
Risk factors(n:2)(n:6)(n:2)(n:3)(n:2)(n:1)
Prior therapy       
Chemotherapy 
Chemoimmunotherapy 
Chemoradiotherapy 
Combination 
Allogeneic       
Related 
Unrelated 
Autologous 
TBI+Cy 
BEAM 
MEL 
BU+Cy 
Unknown 
Chronic GvHD 
Sex       
Female 
Male 
BreastSkinGISUrogenitalLungLymphoma
Risk factors(n:2)(n:6)(n:2)(n:3)(n:2)(n:1)
Prior therapy       
Chemotherapy 
Chemoimmunotherapy 
Chemoradiotherapy 
Combination 
Allogeneic       
Related 
Unrelated 
Autologous 
TBI+Cy 
BEAM 
MEL 
BU+Cy 
Unknown 
Chronic GvHD 
Sex       
Female 
Male 

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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