Abstract
Haploidentical donors are alternative stem cell sources for the patients without matched related and unrelated donors. Finding a full match unrelated donor takes at least 6 months. Most of the patients who have advanced acute leukemia die during this period. Unfortunately, they also loose the chance of haploidentical stem cell transplantation (SCT).
Aim: To report the outcome of six patients whom underwent haploidentical stem cell transplantation using FLAMSA regimen as initial reduction of leukemic burden.
Patients and Treatment: There were six patients (F/M: 3/3) who admitted to transplantation unit between November 2012 and December 2013. Table 1 shows the characteristics of patients. Patients received fludarabine 30mg/m2, ARA-C 2gm/m2, Amsacrine 100 mg/m2 (FLAMSA) consequently 4 days before the intiation of conditioning protocol. According to the conditioning protocol number of the rest days changed (Table 2). For transplantation G-CSF mobilized peripheral blood stem cells were used. No graft manipulation was performed, 5x10e6 CD34+ cells/kg were requested. Graft versus host disease (GVHD) prophylaxis: Cyclophosphamide 50mg/kg/day (+3,+4), Tacrolimus 0.03 mg/kg/day +5 and MMF 3x15mg/kg +6 was started. In the absence of GVHD, MMF was discontinued by day +30, tacrolimus was tapered from day +60 to +100.
Results: All of the patients had active diseases. Three of the six patients died during conditioning. Transplantation related mortality (TRM) was 50%. The other three patients were alive on the day 100. Overall survive (OS) on day 100 was %50. Two patients (22%) lived beyond 6 months. Of these two, one of them has completed the first year (16%) and is still alive without GVHD or disease relaps. Outcome of the patients are shown in Table 2.
Discussion: The patient number is so restricted to draw any conclusions from this report but we know that Allogeneic SCT is the most effective treatment for a variety of hematologic malignancies. The current data suggest that the chosen sequential strategy of intensive chemotherapy followed after a few days of rest by allogeneic SCT has encourging results. Combining this modality with haploidentical transplantation may represent a step forward in the treatment of refractory hematologic malignancies.
Patients’ and donors’ characteristics
| Patient no . | Gender . | Patient Age . | Diagnosis . | Tx no . | PRA . | Donor . | Donor age . |
|---|---|---|---|---|---|---|---|
| 1 | M | 37 | ALL | 1st | Neg | Brother | 44 |
| 2 | F | 47 | ALL | 1st | Neg | Son | 23 |
| 3 | F | 44 | AML | 1st | Neg | Son | 22 |
| 4 | M | 41 | AML | 3rd(2MSD) | Neg | Mother | 65 |
| 5 | F | 26 | AML | 2nd(1MUD) | Neg | Mother | 54 |
| 6 | F | 46 | ALL | 2nd(1MSD) | Neg | Sister | 53 |
| Patient no . | Gender . | Patient Age . | Diagnosis . | Tx no . | PRA . | Donor . | Donor age . |
|---|---|---|---|---|---|---|---|
| 1 | M | 37 | ALL | 1st | Neg | Brother | 44 |
| 2 | F | 47 | ALL | 1st | Neg | Son | 23 |
| 3 | F | 44 | AML | 1st | Neg | Son | 22 |
| 4 | M | 41 | AML | 3rd(2MSD) | Neg | Mother | 65 |
| 5 | F | 26 | AML | 2nd(1MUD) | Neg | Mother | 54 |
| 6 | F | 46 | ALL | 2nd(1MSD) | Neg | Sister | 53 |
M: Male F: Female ALL: Acute lymphoblastic leukemia, AML: Acute myeloblastic leukemia, Tx no: Number of transplantation, PRA: Panel Reactive Antibody, Neg: Negative
MS:Match Sibling Donor, MUD Match Unrelated Donor)
Patients’ outcome
| Patient no . | Conditioning regimen . | Rest day (s) after FLAMSA . | Engraftment PLT 20/ NEU0.5 . | Chimerism on day 30 . | Engraftment failure . | Reinfusion of peripheral blood CD34+ . | GVHD Grade 3-4 . | Comorbid condition . | Status after SCT . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | MEL50mg/m2/day (-5,-4) TBI Gy (-3,-2,-1) | -6 | Yes | Full | Yes | +105.day | Yes | No | Exitus +210 day GVHD |
| 2 | MEL50mg/m2/day (-5,-4) TBI 4Gy(-3,-2,-1) | -6 | Yes | Full | No | No | No | No | Alive +390day |
| 3 | MEL 200mg/m2 (-1) | -3,-2 | No | - | - | - | - | IPA | Exitus+14day Gram negative septicemia |
| 4 | BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) | -9,-8,-7,-6 | No | - | - | - | - | IPA | Exitus+12day Candidemi |
| 5 | MEL 200mg/m2 (-1) | -3,-2 | Yes | Full | Yes | +125day | No | IPA | Alive +240 day |
| 6 | BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) | -9,-8,-7,-6 | No | - | - | NA | Panniculitis IPA | Exitus day 0 |
| Patient no . | Conditioning regimen . | Rest day (s) after FLAMSA . | Engraftment PLT 20/ NEU0.5 . | Chimerism on day 30 . | Engraftment failure . | Reinfusion of peripheral blood CD34+ . | GVHD Grade 3-4 . | Comorbid condition . | Status after SCT . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | MEL50mg/m2/day (-5,-4) TBI Gy (-3,-2,-1) | -6 | Yes | Full | Yes | +105.day | Yes | No | Exitus +210 day GVHD |
| 2 | MEL50mg/m2/day (-5,-4) TBI 4Gy(-3,-2,-1) | -6 | Yes | Full | No | No | No | No | Alive +390day |
| 3 | MEL 200mg/m2 (-1) | -3,-2 | No | - | - | - | - | IPA | Exitus+14day Gram negative septicemia |
| 4 | BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) | -9,-8,-7,-6 | No | - | - | - | - | IPA | Exitus+12day Candidemi |
| 5 | MEL 200mg/m2 (-1) | -3,-2 | Yes | Full | Yes | +125day | No | IPA | Alive +240 day |
| 6 | BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) | -9,-8,-7,-6 | No | - | - | NA | Panniculitis IPA | Exitus day 0 |
BU: Busulfan, Mel: Melfelan, TBI: Total Body Irradiation, PLT 20: Platelet > 20.000 NEU 0.5: Neutrophil>500, GVHD: Graft versus Host Disease, IPA: Invasive Pulmonary Aspergillozis,
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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