Hematologic Diseases, Thrombocytopenia
Conditions
Keywords
Isolated thrombocytopenia, decitabine, rhTPO
Brief summary
Isolated thrombocytopenia is a common and severe complication of HSCT, which often leads to an increased risk of life-threatening hemorrhage, frequent requirement of platelet transfusions and extended hospital stays, representing a challenging clinical problem. Current treatments for thrombocytopenia after HSCT are frequently unsatisfactory in platelet recovery and for preventing potentially fatal bleeding complications. Therefore, it is urgent to explore an effective therapy to improve the outcomes of thrombocytopenia after HSCT. Previous studies have demonstrated that decitabine, a hypomethylating agent, may reduce platelet transfusions in myelodysplastic syndrome (MDS) patients. The investigators conducted an prospective clinical trial to evaluate the safety and efficiency of rhTPO and decitabine in the treatment of thrombocytopenia following HSCT.
Detailed description
Isolated thrombocytopenia is a frequent and severe complication of hematopoietic stem cell transplantation (HSCT). It often leads to an increased risk of life-threatening hemorrhage, frequent requirement of platelet transfusions and extended hospital stays, representing a challenging clinical problem. Current treatments for thrombocytopenia after HSCT, including thrombopoietin, interleukin-11, immunoglobulin, methylprednisolone and rituximab, are frequently unsatisfactory in platelet recovery. Therefore, it is urgent to explore an effective therapy to improve the outcomes of thrombocytopenia after HSCT. Thrombopoietin (TPO) is a cytokine that drives thrombopoiesis by stimulating the differentiation of stem cells into megakaryocytes and promoting megakaryocyte proliferation and polyploidization. Decitabine was approved for the treatment of myelodysplastic syndrome (MDS) as a DNA methylation inhibitors. Studies in vitro show that decitabine enhances platelet release and megakaryocyte maturation. Here, the investigators performed a prospective clinical trial, in order to investigate the safety and efficiency of rhTPO and decitabine in the treatment of thrombocytopenia following HSCT.
Interventions
DRUGDecitabine
Decitabine
DRUGrhTPO
rhTPO
OTHERConventional Treatment
immunoglobulin, glucocorticoid etc
Sponsors
Peking University People's Hospital
Nanfang Hospital, Southern Medical University
Ruijin Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Qilu Hospital of Shandong University
Children's Hospital of Soochow University
Fujian Medical University Union Hospital
Hebei Yanda Ludaopei Hospital
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Platelet count ≤ 30 × 109/L persistently at day 60 post-HSCT or later; 2. Neutrophil and hemoglobin were well recovered; 3. Full donor chimerism was achieved; 4. No response to conventional treatments (e.g. thrombopoietin, immunoglobulin, glucocorticoid alone or in combination) for a duration of at least 4 weeks;
Exclusion criteria
1. Patients with malignancy relapse; 2. Active infections; 3. Grade Ⅲ-Ⅳ acute GVHD or severe chronic GVHD according to National Institute of Health criteria; 4. Severe organ damage; 5. Thrombosis requiring treatment; 6. Received decitabine following the current transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Platelet Count Recovery | Up to 4 weeks after the treatment | Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Megakaryocyte Count | Up to 4 weeks after the treatment | The total number of megakaryocytes as well as the platelet-shedding megakaryocytes of bone marrow smears (per cm2) was counted and cross-checked by blinded observers. |
Countries
China
Participant flow
Recruitment details
Two participants from different institutions submitted the applications at the same time when there was only one quota left. Both of them met the inclusion criteria and were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group 1 Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with rhTPO 15000 U daily subcutaneously beginning on day 4 and continuing until the response was achieved or the time of initial evaluation. | 30 |
| Experimental Group 2 Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone. | 30 |
| Control Group Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination. | 31 |
| Total | 91 |
Baseline characteristics
| Characteristic | Control Group | Total | Experimental Group 2 | Experimental Group 1 |
|---|---|---|---|---|
| ABO compatitibilty ABO matched | 18 Participants | 46 Participants | 13 Participants | 15 Participants |
| ABO compatitibilty ABO mismatched | 13 Participants | 45 Participants | 17 Participants | 15 Participants |
| Age, Continuous | 36 years | 31 years | 36 years | 30 years |
| Conditioning Busulfan / cyclophosphamide | 29 Participants | 82 Participants | 27 Participants | 26 Participants |
| Conditioning Others | 2 Participants | 9 Participants | 3 Participants | 4 Participants |
| Diagnosis Acute lymphocytic leukemia | 11 Participants | 29 Participants | 10 Participants | 8 Participants |
| Diagnosis Acute myeloid leukemia | 12 Participants | 41 Participants | 14 Participants | 15 Participants |
| Diagnosis Chronic myeloid leukemia | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Diagnosis Myelodyplastic syndrome | 4 Participants | 13 Participants | 4 Participants | 5 Participants |
| Diagnosis Non-Hodgkin lymphoma | 3 Participants | 5 Participants | 0 Participants | 2 Participants |
| Enrollment time | 79 days | 99 days | 105 days | 103 days |
| Megakaryocyte counts at enrollment | 3.1 cells/cm^2 | 3.0 cells/cm^2 | 3.2 cells/cm^2 | 2.9 cells/cm^2 |
| Mononuclear cell infused | 9.40 10E8/kg | 10.04 10E8/kg | 10.50 10E8/kg | 9.78 10E8/kg |
| Neutrophils recovery | 13 days | 12 days | 12 days | 12 days |
| Platelet counts at enrollment | 17 10E9 platelets/L | 15 10E9 platelets/L | 12 10E9 platelets/L | 14 10E9 platelets/L |
| Race and Ethnicity Not Collected | — | 0 Participants | — | — |
| Region of Enrollment China | 31 Participants | 91 Participants | 30 Participants | 30 Participants |
| Sex: Female, Male Female | 15 Participants | 32 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Male | 16 Participants | 59 Participants | 18 Participants | 25 Participants |
| Transplant Donor Haploidentical donor | 21 Participants | 64 Participants | 20 Participants | 23 Participants |
| Transplant Donor Matched related donor | 6 Participants | 19 Participants | 8 Participants | 5 Participants |
| Transplant Donor Matched unrelated donor | 4 Participants | 8 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 0 / 30 | 1 / 31 |
| other Total, other adverse events | 8 / 30 | 5 / 30 | 7 / 31 |
| serious Total, serious adverse events | 4 / 30 | 1 / 30 | 3 / 31 |
Outcome results
Primary
Number of Participants With Platelet Count Recovery
Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days.
Time frame: Up to 4 weeks after the treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group 1 | Number of Participants With Platelet Count Recovery | 20 Participants |
| Experimental Group 2 | Number of Participants With Platelet Count Recovery | 22 Participants |
| Control Group | Number of Participants With Platelet Count Recovery | 6 Participants |
Secondary
Megakaryocyte Count
The total number of megakaryocytes as well as the platelet-shedding megakaryocytes of bone marrow smears (per cm2) was counted and cross-checked by blinded observers.
Time frame: Up to 4 weeks after the treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group 1 | Megakaryocyte Count | 6.7 cells/cm^2 |
| Experimental Group 2 | Megakaryocyte Count | 7.5 cells/cm^2 |
| Control Group | Megakaryocyte Count | 3.3 cells/cm^2 |