Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Early evaluation of CAR-T cell therapy response in R/R DLBCL patients using 18F-FDG PET/CT.

OBJECTIVE: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy provides a durable response in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The role of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early evaluation of response in patients with that immunotherapy was evaluated. SUBJECTS AND METHODS: Three separate 18F-FDG PET/CT examinations of 53 patients (29 males, 24 females; median 62 years old) with R/R DLBCL were conducted; before bridging therapy [time of decision (TD)], before CAR-T (tisagenlecleucel, n=37; lisocabtagenemaraleucel, n=16) infusion [time of CAR-T infusion (IT)], and one month (M1) after CAR-T infusion. Response was evaluated based on the Deauville 5-point scale and Lugano criteria. RESULTS: Among 21 patients (39.6%) with complete metabolic response (CMR) at IT-PET, 20 were able to continue CMR, while one showed progression at M1-PET. Among 32 patients (60.4%) with non-CMR at IT-PET, 12, 8, 4, and 8 showed CMR, partial metabolic response (PMR), (non-metabolic response (NMR), and progressive metabolic disease (PMD), respectively, at M1-PET as compared with IT-PET. Evaluations of M1-PET as compared with baseline TD-PET indicated 32, 7, 5, and 9 patients with CMR, PMR, NMR, and PMD, respectively. After a median 10.1 months, 26 patients showed progression and 13 had died from DLBCL. The 32 who achieved CMR showed significantly longer progression-free (P<0.0001) and overall survival (P<0.0001) periods as compared to the 21 non-CMR patients. CONCLUSION: Fluorine-18-FDG PET/CT findings obtained one month after CAR-T cell therapy showed accuracy for early response evaluation and prediction of progression in patients with R/R DLBCL.

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

RhD mismatch does not affect haematopoietic recovery, graft-versus-host disease and survival in allogeneic haematopoietic cell transplantation: A Japanese registry-based study.

BACKGROUND AND OBJECTIVES: ABO blood group mismatch between the donor and the recipient can affect the success of the transplant as well as problems with the red blood cells during allogeneic haematopoietic cell transplantation (HCT). However, the impact of the Rhesus (Rh) D mismatch on transplant outcomes in allogeneic HCT has been poorly elucidated. MATERIALS AND METHODS: We retrospectively evaluated the impact of the RhD mismatch on post-transplant outcomes in 64,923 patients who underwent allogeneic HCT between 2000 and 2021 using a Japanese registry database. RESULTS: Out of the whole group, 64,293, 322, 270 and 38 HCTs were done when the recipient or donor was RhD-mismatched with (+/+), (-/+), (+/-) or (-/-) combinations. The difference in RhD between recipient/donor (-/+), (+/-) and (-/-) did not affect haematopoietic recovery, acute and chronic graft-versus-host disease (GVHD), overall survival (OS), non-relapse mortality (NRM) or relapse when RhD (+/+) was used as the reference group in multivariate analysis. CONCLUSION: Our registry-based study demonstrated that RhD mismatch between recipient and donor did not significantly impact haematopoietic recovery, GVHD, OS, NRM or relapse after allogeneic HCT. These data suggest that RhD mismatches may not need to be avoided for recipient and donor combinations in allogeneic HCT.

Pretransplantation predictors of survival in nonremission acute myeloid leukemia treated with haploidentical transplantation using steroid-based GVHD prophylaxis.

Haploidentical hematopoietic cell transplantation (HCT) using glucocorticoids for acute graft-versus-host disease prophylaxis (GC-haplo) may become a curative treatment option for nonremission acute myeloid leukemia (AML). This retrospective study aimed to identify pre-HCT predictors of survival in a cohort of 97 nonremission AML treated with GC-haplo in Hyogo Medical University Hospital between 2010 and 2020. Relapse and primary induction failure included in 70 (72%) and 27 (28%) patients, respectively. Sixty-one patients (63%) had undergone previous HCT. Multivariate analysis revealed that ≤ 6 months' duration between first complete remission (CR1) and first relapse (Rel1) (CR1-Rel1 interval) (hazard ratio 2.11, 95% confidence interval [CI] 1.15-3.89, P = 0.016) and serum albumin before starting the conditioning treatment of ≤ 3.5 g/dL (hazard ratio 1.80, 95%CI 1.09-2.96, P = 0.022) as risk factors for overall survival. Among three groups categorized according to serum albumin and CR1-Rel1 interval, the best 3-year overall survival was observed in patients with albumin > 3.5 g/dL and CR1-Rel1 interval > 6 months or primary induction failure (50.2%, 95%CI 28.9%-68.3%, P < 0.001), revealing that survival could be predicted using albumin and past CR duration in patients with very high-risk AML not in remission before GC-haplo.

Individualized rabbit anti-thymocyte globulin dosing in adult haploidentical hematopoietic cell transplantation with high-risk hematologic malignancy: Exposure-response analysis and population pharmacokinetics simulations.

Hematopoietic cell transplantation (HCT) for hematologic malignancies with non-remission disease and/or prior post-transplant relapse have poor relapse-free survival. We previously demonstrated the efficacy of haploidentical reduced-intensity HCT regimen with glucocorticoid-based graft-versus-host disease (GVHD) prophylaxis. We recently showed a possible association between rabbit antithymocyte globulin (rATG) exposure and acute GVHD (aGVHD) risk, leading to hypothesize that optimization of rATG exposure may further improve this regimen. We retrospectively examined the exposure-response association of rATG and key clinical outcomes post haploidentical HCT. We subsequently developed an individualized rATG dosing that optimizes rATG exposure using a previously developed population pharmacokinetic model. Of the 103 patients analyzed, the median age was 47 years (range: 17-70) and majority had a non-remission disease prior to HCT (88%). rATG concentration on day 0 of HCT (Cday_0 ) was the strongest predictor of Grade 2-4 aGVHD through day +100. Patients with Cday_0 ≥ 20 µg/mL had an approximately 3-fold lower risk of Grade 2-4 aGVHD (hazard ratio [HR]: 0.32, 95% confidence interval [CI]: 0.16, 0.62) and Grade 3-4 aGVHD (HR: 0.33, 95% CI: 0.16, 0.68) as well as an approximately 2-fold lower risk of overall mortality (HR: 0.47, 95% CI: 0.28, 0.77) and relapse (HR: 0.50, 95% CI: 0.26, 0.94). In conclusion, this reduced-intensity haploidentical HCT regimen with exposure-optimized rATG may provide a promising option to patients undergoing high-risk HCT for hematologic malignancy. The developed rATG dosing warrant prospective validation.

A case of non-Hodgkin lymphoma of the upper gingiva with minimal residual disease detected in cryopreserved ovarian tissue: A case report.

Recently, more than 200 live births following ovarian tissue cryopreservation (OTC) and transplantation in cancer survivors have been reported worldwide. However, cancer survivors with minimal residual disease (MRD) in cryopreserved ovarian tissue are at the risk of relapse through the graft. Here, we report a rare case of a 19-year-old female patient with non-Hodgkin lymphoma who had MRD in the ovary harvested for OTC. The patient was diagnosed with aggressive B-cell lymphoma after gingival biopsy. The 18F-fluoro-2-deoxy-D-glucose positron emission tomography scan performed before OTC showed no viable lesions in either ovary. However, on histological evaluation, we detected infiltration of lymphoma cells in the ovary. Informed consent about MRD is required even if there is no evidence of MRD in the ovary before OTC. Patients whose cryopreserved ovaries have MRD may require the development of alternative assisted reproductive technologies such as in vitro growth or artificial ovary.

Allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia not in remission.

Allogeneic hematopoietic cell transplantation (HCT) is the last option for long-term survival for patients with chemotherapy-refractory acute myeloid leukemia (AML). By using the Japanese nationwide registry data, we analyzed 6927 adults with AML having undergone first allogeneic HCT while not in complete remission (CR) between 2001 and 2020. The 5-year overall survival (OS), relapse, and non-relapse mortality (NRM) rates were 23%, 53%, and 27%, respectively. Multivariate analysis identified several factors predictive of OS mainly through their effects on relapse (cytogenetics, percentage of blasts in the peripheral blood, and transplantation year) and NRM (age, sex, and performance status). As regards disease status, relapsed disease was associated with a higher risk of overall mortality than primary induction failure (PIF). The shorter duration of the first CR increased the risks of relapse and overall mortality for the relapsed group, and the longer time from diagnosis to transplantation did so for the PIF group. Our experience compiled over the past two decades demonstrated that >20% of patients still enjoy long-term survival with allogeneic HCT performed during non-CR and identified those less likely to benefit from allogeneic HCT. Future efforts are needed to reduce the risk of posttransplant relapse in these patients.

Impact of cytogenetic abnormalities in symptomatic multiple myeloma; a Japanese real-world analysis from Kansai Myeloma Forum.

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.

Real-world data on induction therapy in patients with transplant-ineligible newly diagnosed multiple myeloma: retrospective analysis of 598 cases from Kansai Myeloma Forum.

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.

Population Pharmacokinetics of Total Rabbit Anti-thymocyte Globulin in Non-obese Adult Patients Undergoing Hematopoietic Cell Transplantation for Hematologic Malignancy.

BACKGROUND AND OBJECTIVES: Rabbit anti-thymocyte globulin (rATG), a therapeutic polyclonal antibody against human T cells, is commonly used in conditioning therapy prior to allogeneic hematopoietic cell transplantation (HCT). Previous studies successfully developed an individualized rATG dosing regimen based on "active" rATG population PK (popPK) analysis, while "total" rATG can be a more logistically favorable alternative for early HCT outcomes. We conducted a novel popPK analysis of total rATG. METHODS: Total rATG concentration was measured in adult human-leukocyte antigen (HLA) mismatched HCT patients who received a low-dose rATG regimen (total 2.5-3 mg/kg) within 3 days prior to HCT. PopPK modeling and simulation was performed using nonlinear mixed effect modeling approach. RESULTS: A total of 504 rATG concentrations were available from 105 non-obese patients with hematologic malignancy (median age 47 years) treated in Japan. The majority had acute leukemia or malignant lymphoma (94%). Total rATG PK was described by a two-compartment linear model. Influential covariate relations include ideal body weight [positively on both clearance (CL) and central volume of distribution], baseline serum albumin (negatively on CL), CD4+ T cell dose (positively on CL), and baseline serum IgG (positively on CL). Simulated covariate effects predicted that early total rATG exposures were affected by ideal body weight. CONCLUSIONS: This novel popPK model described the PK of total rATG in the adult HCT patients who received a low-dose rATG conditioning regimen. This model can be used for model-informed precision dosing in the settings with minimal baseline rATG targets (T cells), and early clinical outcomes are of interest.

Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan.

For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 104 /µL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3-24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105 /µL; p = 0.022) or low CD4/CD8 ratios (

Efficacy of elotuzumab for multiple myeloma in reference to lymphocyte counts and kappa/lambda ratio or B2 microglobulin.

Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower ß2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/µL), non-deviated κ/λ ratio (0.1-10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/µL and 1 point for < 1400/µL) and κ/λ ratio (0 points for 0.1-10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.

Measurable Residual Disease Assessment Using Next-Generation Flow in Patients With Relapsed and Refractory Multiple Myeloma Treated With a Combination of Carfilzomib, Lenalidomide, and Dexamethasone.

BACKGROUND/AIM: Carfilzomib, lenalidomide, and dexamethasone (KRD) therapy is widely used for patients with relapse/refractory multiple myeloma (RRMM). However, the response in patients who underwent assessment for measurable residual disease (MRD) has not been elucidated in a prospective study. We aimed to clarify the response rate and outcome of KRD therapy in patients in RRMM, including those with MRD. PATIENTS AND METHODS: Twenty-one consecutive RRMM patients treated with KRD at 4 Japanese Centers between September 2016 and October 2018 were enrolled and assessed for MRD in the bone marrow (cut-off: 1×10-5) using the EuroFlow-next-generation flow (NGF) method. RESULTS: The median number of therapy lines before KRD was 3 (range=1-6), and the median number of KRD cycles was 4 (range=1-22). As the best overall response post-KRD therapy, 52% (11/21) of patients achieved a MRD negative complete response, 71% (15/21) achieved stringent complete response/complete response, and 14% (3/21) achieved a very good partial response. MRD negativity was achieved in 12 of 16 (75%) and 14 of 21 (67%) patients during and after KRD treatment, respectively. The 2-year progression-free survival and overall survival from the start of KRD therapy were 100% and 100%, respectively, in MRD-positive cases and 88% and 100%, respectively, in MRD-negative cases (median follow-up=1.8 years). Grade 3/4 toxicities were reported in 15 patients (71%), with thrombocytopenia being the most frequent toxicity (6 patients, 29%). CONCLUSION: This is the first study that prospectively assessed MRD of patients with RRMM after KRD therapy. KRD treatment achieved a high MRD negativity rate and good outcomes with manageable toxicities.

Monocyte or white blood cell counts and ß2 microglobulin predict the durable efficacy of daratumumab with lenalidomide.

Background: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. Objectives: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. Design: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. Methods: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. Results: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower ß2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. Conclusion: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/µl; 1 point for <200/µl) or WBC counts (0 points for ⩾3500/µl; 1 point for <3500/µl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.

Severe acute heart failure during or following cytokine release syndrome after CAR T-cell therapy.

Although cardiac dysfunction after chimeric antigen receptor (CAR) T-cell therapy has been increasingly reported, the underlying dynamics and pathogenesis are not well documented. Herein, we describe the clinical presentation and treatment for two patients who developed severe acute heart failure after CAR T-cell therapy. Both cases shared several common characteristics, including the bone marrow involvement at the time of CAR T-cell therapy and early onset of cytokine release syndrome (CRS) with fever developing on the day of CAR T-cell infusion. Patients with early onset and/or severe CRS should be carefully monitored for the possibility of heart failure.

Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis.

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.

T-cell lymphoma, B-cell lymphoma, and myelodysplastic syndrome harboring common mutations: Trilineage tumorigenesis from a common founder clone.

A 64-year-old man with angioimmunoblastic T-cell lymphoma (AITL) subsequently developed diffuse large B-cell lymphoma (DLBCL) and myelodysplastic syndrome (MDS). Genomic profiling of AITL, DLBCL, and MDS samples revealed that the tumor cells from all samples shared common mutations in TET2 and DNMT3A. In addition, the IDH2 mutation was observed in AITL, and TP53 mutation was observed in DLBCL and MDS. These findings illustrate the clonal relationship between AITL and DLBCL in addition to AITL and MDS, with the latter being increasingly reported. The present findings strongly support the theory of multistep and multilineage tumorigenesis from a common founder clone.