Outline History Definition Rationale Procedure Indications Our data Summary
History of Blood and Marrow Transplantation in the Philippines 1990 1 st marrow transplant at the NKTI 2001 1 st peripheral blood stem cell transplant at NKTI 2002 St Luke’s Medical Center (SLMC) 2002 Asian Hospital Medical Center (AHMC) 2005 1 st autologous stem cell transplant at AHMC 2005 1 st cord blood transplant at SLMC
The transfusion of the immature progenitor stem cells derived from a donor to the recipient (allogeneic); OR stem cells previously harvested from the patient (autologous). It is NOT an operation / surgical procedure.
Stem cells Bone marrow 2 to 5 x 10 8 TNC/kg weight of recipient with the maximum volume dictated by the weight of the donor (20ml BM aspirate/kg) can be stored at room temperature for up to 24hrs until infusion into the recipient or cryopreserved Peripheral blood 2.0 to 5.0 x 10 6 CD34 + cells/kg for auto/allo transplants can be stored at 4 C overnight or cryopreserved with dimethyl sulfoxide (DSMO) Umbilical cord 3.7 x 10 6 TNC/kg recipient body weight can be stored at 4 C or 25 C for up to three days or cryopreserved with DSMO
Two kinds Allogeneic: Donor –Matched or partially mismatched sibling –Unrelated –Cord blood Autologous: No donor –Stem cells are harvested from patient
Allogeneic transplant involves the transfer of stem cells from donor to recipient to permanently replace all hematopoietic cells eradicate malignant cells with high dose chemotherapy +/- radiotherapy sufficient immunosuppression of the host to allow growth of the allograft immune mediated graft vs leukemia/lymphoma or graft vs tumor effect
Autologous transplant Increasing the dose of some chemotherapeutic agents may result in large increase in tumor cell kill Transfusing previously harvested stem cells of the patient will guarantee bone marrow recovery
Schema -8 admit to hospital -7 Total body Irradiation -6 Total body Irradiation -5 Total body Irradiation -4 Total body Irradiation; Donor starts GCSF -3 Cytoxan (60mg/kg) -2 Cytoxan (60mg/kg) -1 Rest day and start cyclosporine IV 0 Harvest and infusion of stem cells +1 Methotrexate 15mg/mm +3 Methotrexate 10mg/mm +6 Methotrexate 10mg/mm +11 Methotrexate 10mg/mm
The transplant Day-8 admit Day-7 Total body irradiation Day -6 Total Body irradiation Day -5 Total body irradiation Day-4 etoposide 60mg/kg IV Day-3 rest Day-2 cytoxan 100mg/kg IV Day-1 rest Day 0 infusion of stem cells Day+5 begin GSCF 5mg/kg/day Day+10 marrow recovery or engraftment
Allogeneic BMT in Pediatric AML Indications: All except Down’s syndrome t(8;21) t(15;17) inv 16
Allogneic BMT in Pediatric ALL Indications: t(9;22)t(4,11) 3 rd CR or higher relapse on therapy or w/in 12 months of end of therapy May be offered: > 28 days to achieve CR 2 nd CR, relapse > 12 months of end of therapy
Allogneic BMT in adult ALL Poor risk features WBC > 25,000 T(9;22) t(8;14) t(4;11) Age > 30y/o Extramedullary disease Requiring more than 4 weeks to achieve a CR
Allogeneic BMT in adult AML Prognostic indicators that predict outcome of standard chemotherapy based on cytogenetic abnormalities. favorable: t(8;21) t(15;17) inv 16 Intermediate: del y; normal karyotype; 11q23 Poor: all others
Nausea and Vomiting Nutrition Mouth Sores Diarrhea Infection Renal complications Veno-Occlusive disease of the liver (VOD) Pancytopenia Graft Rejection Acute Graft vs Host Disease Rash Pulmonary complications Death
Nausea and Vomiting –More common during the early part of transplant –Round the clock anti emetic medications –During the recovery phase, nausea / vomiting / abdominal pain (cramps) / diarrhea, the patient may have graft vs host disease (GVHD).
Nutrition –Low bacteria diet: no fresh fruit and vegetables; served hot; no left over; tray should be clean; –Appetite diminishes after chemotherapy –Total parenteral nutrition until patient can eat.
Mouth Sores –Mouth wash (nystatin and biotene) –Morphine pushes or drip when severe (face will be swollen) –Thrush
Bacterial Infections –Gram negative –Gram positive (central line or skin); patient should shower or sponge bath daily. –Antibiotics: third generation cephalosporin and vancomycin Fungal –Pulmonary (aspergillus) –Yeast –Amphoteric B prophylaxis Viral –Herpes zoster –Acyclovir IV
Prevention Isolation room : positive pressure Strict hand washing Mask No need for gown or gloves unless patient is positive for clostridum defficile
Renal Complications –Renal insufficiency –Drugs: cyclosporine, vancomycin, amphotericin B) –Monitor I & 0 accurately every 12 hours. Balance fluid I & 0. lasix IV given prn.
Liver Complications –Veno-Occlusive disease of the liver (VOD) Water retention Tender liver Elevated bilirubin Elevation in bilirubin and SGPT and SGOT –Medications: cyclosporine, TPN –GVHD
Pancytopenia –Blood and platelet transfusion –Platelet apheresis is always used –Blood and platelets should always be available, filtered and irradiated.
Graft rejection –Engraftment occurs between two to three weeks after transfusion of stem cells –Recipient develops antibodies against the HLA antigen of the donor. –Incidence increases in heavily transfused patients. –Prior transfusions without filter and random donor platelets used
Graft versus host disease –Occurs when donor stem cells recognizes the body of the recipient as foreign and attacks the body. –Acute GVHD occurs during engraftment: diarrhea, elevated bilirubin and rash –GVHD prophylaxis: cyclosporine IV, methotrexate IV
BMT Data December 2002 to April 2007 27 stem cell transplants –22 allogeneic –5 autologous Ages: 8 months to 66 years old Sex: 17M and 10F Transplant Regimen: –Chemotherapy only: 21 –Fractionated total body irradiation + chemo: 6 GVHD prophylaxis: –CSA + Methotrexate 17 –CSA + Cellcept 5
BMT Data: Donor Sex –Same sex: 10 –Opposite sex: 12 HLA match –Full sibling: 21 –Mismatch: 1(HLA 4/6 from father)
BMT Data 22 allogeneic –Acute myelogenous Leukemia 10 1 st CR 7 2 nd CR 1 Induction failure 2 –Acute lymphoblastic leukemia 4 1 st CR 1 > 1 st CR 3 –Myelodysplastic syndrome 4 –Chronic myelogenous leukemia 1 –Severe aplastic anemia 1 –Thalassemia 1 –Metastatic (lung & bones) renal cell cancer 1
BMT Data 5 Autologous –3 multiple myeloma –1 relapsed hodgkin’s disease –1 acute myelogenous leukemia in 2 nd CR
Results Allogeneic Harvested stem cells: mean 7 x 10 6 CD34 + cells / kg BW of patient Range: 2.9 to 23.6 x 10 6 CD34 + cells Days of harvest: mean 2 days Range 1 to 4 days Autologous Harvested stem cells: mean 5.1 x 10 6 CD34 + cells / kg BW of patient Range: 3.2 to 8.1 x 10 6 CD34 + cells Days of harvest: mean 2 days Range 1 to 4 days
Results Engraftment (allo and auto) –Mean 13 days –Range: 10 to 18 days
Rejection Acute: Patient with AML 1 st CR did not engraft at all. Positive antibodies against HLA. Was salvaged with a second transplant using same donor. Currently doing well and off immuno drugs Delayed: Patient with thalassemia. Graft rejection after 1 year. Autologous recovery of marrow. Transfusion dependent.
Acute Graft Vs Host Disease (AGVHD) in BMT Manifestation of alloreactivity and occurs when mature T cells are transferred to hosts expressing histocompatibility differences Donor CD4+ and CD8+ target major tissues of the skin, liver and intestinal tract
Acute Graft vs Host Disease (GVHD) n = 15/22 Grade# of pts 15 27 32 41
Causes of GVHD Causes HLA disparity Conditioning regimen Sex mismatch Age Parous donor Peripheral blood vs marrow
Infection 8 had either gram (+) or gram (-) bacterial infection 1 had recurrence of PTB during transplant. He was an auto transplant patient with relapsed hodgkin’s disease, (+) history of treated PTB 4 had herpes zoster, months after 1 had anal warts, months after
Cytomegalovirus (CMV) 9/14 developed (+) CMV blood culture within 100 days of transplant. They were successfully treated with ganciclovir for six weeks. Risks of developing CMV: –HLA mismatch –AGVHD –(+) serum CMV antibody
Mortality n = 11 Infection (Gm negative septic shock) 2 –10 and 11 days post transplant – history of prior infections – poor performance status Severe AGVHD of the GIT 1 Relapse disease 8 –2 ALL > 1 st CR –3 myelodysplastic syndrome –1 AML induction failure –1 AML auto –1 multiple myeloma auto
survival Allogeneic: 13/22 Autologous: 3/5 16/27 survivors 1 st patient transplanted is now 4yrs and 5 months post transplant Data may change in time –wait for 2 to 3 years
Improve outcome Education and information –Can be done in our country –Dispel myths Not a surgical procedure Harvesting stem cells is not a painful procedure Maximum hospital stay 6 weeks Live a normal life Screen candidates Early transplant and not later on (not a last resort)