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Volume: 15 Issue: 1 February 2017 - Supplement - 1

FULL TEXT

First Report on Stem Cell Transplant From Iraq

The Iraqi Bone Marrow Transplantation Center is located in the medical city complex of Bab Almuadham in Baghdad, Iraq. It was established on March 11, 2002, and performed its first mini-allotransplant for acute myeloid leukemia on January 24, 2003. Among 16 patients who received hematopoietic stem cell transplant between January 2003 and January 2010, one patient underwent allogeneic bone marrow transplant for acute myeloid leukemia and 15 patients received autologous bone marrow transplant for the following indications: 5 had multiple myeloma, 9 had lymphoma (8 with Hodgkin disease and 1 with non-Hodgkin lymphoma), and 1 had rhabdomyosarcoma. Median age was 34 years (range, 10-56 y), and our patient group included 8 females and 8 males. Of the 16 patients, 12 are still alive. The mortality rate was 25% as measured during our follow-up from 2 to 96 months. Of the 9 patients with lymphoma, 1 died and 2 relapsed after transplant. Therefore, our survival rate in lymphoma was 88%, with progression-free survival in lymphoma ranging from 2 to 66 months (mean survival of 13 mo, mode of 13 mo). For the 5 patients with multiple myeloma who received transplants, 1 died and 2 relapsed, with effective-free survival of 6 to 13 months. Our results show that high-dose chemotherapy followed by autologous stem cell transplant can induce long-term disease control in this cohort of patients with refractory or advanced Hodgkin disease; progression-free survival for our cohort was 50%, with survival comparable to those reported in the literature.


Key words : First, Iraq, Stem cell transplant

Introduction

The bone marrow transplant center in Iraq is located in the medical city complex of Bab Almuadham in Baghdad and was established on March 11, 2002. The center performed its first mini-allotransplantation for acute myeloid leukemia on January 24, 2003. That patient died in February 2003 because of multiorgan failure due to early relapse. Subsequently, no further transplants were performed after the United States invasion in Iraq in March 2003.

Marino Andolina, a prominent pediatrician and head of a bone marrow transplant unit in Trieste, Italy, has repeatedly visited Iraq to help support pediatric hospitals in Baghdad and other governorates. A decision was made, with the cooperation of Dr. Andolina, to perform a transplant procedure (autograft for relapsed Hodgkin disease) on August 13, 2004. Subsequently, the safety situation became critical again, and the center stopped doing transplants until another was performed on June 18, 2008, when security had improved. This multiple myeloma patient was our third autologous stem cell transplant and showed engraftment at day +20. This procedure was followed by other cases.

The importance is that this procedure is only done in this center in all of Iraq. This center helps treat different onco-hematology patients and has opened its care to treating different congenital blood diseases. Since 2003, it is the first and only center in Iraq established with a comprehensive hematopoietic stem cell transplant program.

Materials and Methods

Among 16 patients who received hematopoietic stem cell transplants between January 2003 and January 2010, one patient underwent allogeneic bone marrow transplant for acute myeloid leukemia, and 15 patients underwent autologous bone marrow trans­plant for the following indications: 5 had multiple myeloma, 9 had lymphoma (8 with Hodgkin disease and 1 with non-Hodgkin lymphoma), and 1 had rhabdomyosarcoma. Median age was 34 years (range, 10-56). Our cohort included 8 females and 8 males.

Indications and characteristics of allogeneic bone marrow transplant Allogeneic bone marrow transplant was performed for de novo acute myeloid leukemia in 1 patient in complete remission from an HLA-identical sibling. Conditioning regimen was a combination of cyclophosphamide and fludarabine.

For the autologous patients, high-dose melphalan with noncryogenic procedure was used in all patients, including those with lymphoma and multiple myeloma. The melphalan dose was approximately 180 mg/m2. The engraftment period (from day 0 until an absolute neutrophil count of 500 was obtained) ranged from 13 to 29 days, with mean of 18 days and mode of 18 days.

Our conditioning protocol in all patients was melphalan alone, except the allogeneic patients received a combination of fludarabine and cyclo­phosphamide. A noncryogenic protocol was used. The product was reinfused 24 hours after chemotherapy.

To assesses response to autologous stem cell transplant, we performed clinical examinations and other laboratory and radiologic tests, including computed tomography scan 3 months after transplant. Subsequent control scans were every 6 months for the first 2 years and then yearly afterward. Patients showing no evidence of disease on computed tomography scans were considered to have complete response. Those achieving a greater than 50% reduction in tumor mass were defined as having a partial response, and those with less than 50% reduction in tumor mass were defined as being nonresponders.

Results

Of 16 patients, 12 are still alive. Mortality rate was 25% during the total follow-up from 2 to 96 months. Of the 9 patients with lymphoma, 1 died and 2 relapsed after transplant. Therefore, our survival rate in lymphoma was 88%; progression-free survival in lymphoma ranged from 2 to 66 months, with mean survival of 13 months (mode of 13 mo).

Transplant-related mortality for the lymphoma patients was 0 as no patient died early after transplant. For the 5 patients with myeloma, 1 died and 2 relapsed after transplant, with effective-free survival of 6 to 13 months. The 1 patient with multiple myeloma who died had died soon after transplant (from cardiac insult). Of the 4 patients with myeloma who survived, 2 relapsed. Double transplant is the usual agreed-on procedure for multiple myeloma; however, all of our myeloma patients received only 1 transplant.

Transplant-related mortality for myeloma occurred in 1 patient (20%). Reconstitution was obtained in 15 patients, as 1 patient died on day 5 after transplant because of cardiac insult. Further mortality results are as follows: 4 patients died from January 2003 to January 2010. Patients included 1 female patient with M2 acute myeloid leukemia who died 1 month after transplant from multiorgan failure due to early relapse after engraftment. Other patients included a pediatric patient with rhabdo­myosarcoma who died 4 months after transplant because of relapse, a 57-year-old patient with multiple myeloma relapse who died early after conditioning because of myocardial infarction, and a 33-year-old patient who died because of bleeding after early relapse 3 months after engraftment, with death occurring 9 months after transplant. Overall transplant-related mortality showed 2 during the first 100 days and 2 occurring late.

Relapse occurred in 7 of 16 patients. Early relapse in the first 6 months occurred in 5 patients.

Regarding cell dose, cell doses ranged from 0.5 to 2.25 per kg mononuclear cells. Stem cell sources included 8 having peripheral blood stem cells, 3 having bone marrow harvests under general anesthesia, and 5 having both procedures. Platelet engraftment occurred 13 to 30 days after transplant (mode of 20 d and mean of 20 d).

Other noted data included most lymphoma cases having more than 2 complete responses before transplant, no patients having bone marrow involvement, and days of fever ranging from 0 to 10 days (mean of 5 d).

Discussion

Because our stem cell transplant results include a short study period, our results cannot be fully conclusive. Most patients underwent transplants between June 2008 and January 2010. Therefore, drawing conclusions regarding our transplant results, with lymphoma comprising the indication in most of our patients (due to relapsed Hodgkin disease), is difficult. It is well known that many factors can influence the results of treatment by autotransplant, and those factors include frequency of relapse before salvage chemotherapy and transplant and disease bulk before transplant.1,2

Most of our patients received many cycles of chemotherapy because stem cell transplant was not available in Iraq, and most patients were in complete response more than 3 times. These factors usually lead to reduced response to transplant and reduce the survival rate after transplant. Many steps are being taken to enhance optimal care before and after transplant, including proper salvage chemotherapy to induce remission in 1 or 2 sessions and getting the maximum cell product that we can collect through bone marrow recovery or peripheral stem cell collection.

Our cohort included 8 with Hodgkin lymphoma who underwent the transplant procedure from August 2004 to January 2010. Only one of these transplants was conducted in 2004; the remaining underwent transplants after June 2008. From these 8 patients, mortality occurred in 1 patient and relapse occurred in 4 patients, meaning 50% relapse in less than 2 years and 1 patient dying after relapse. It is noteworthy that the most important years after transplant are the first 2 years; therefore, our response rate is comparable to other centers.

Our results show that high-dose chemotherapy followed by an autologous stem cell transplant can induce long-term disease control in this cohort of patients with refractory or advanced Hodgkin disease. Progression-free survival of the whole series was 50%, a rate comparable to those reported by other groups.1-5


References:

  1. Longo DL, Duffey PL, Young RC, et al. Conventional dose salvage combination chemotherapy in patients relapsing with Hodgkin’s disease after combination chemotherapy: the low probability for cure. J Clin Oncol. 1992;10:210-218.
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  2. Chopra R, McMillan AK, Linch DC, et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor risk Hodgkin’s disease. A single center eight year study of 155 patients. Blood. 1993;81:1137-1145.
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  3. Reece DE, Connors JM, Spinelli JJ, et al. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin’s disease in first relapse after combination chemotherapy. Blood. 1994;83:1193-1199.
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  4. Nademanee A, O´Donell MR, Snyder DS, et al. High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin’s disease: results in 85 patients with analysis of prognostic factors. Blood. 1995;85:1381-1390.
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  5. Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, Horning SJ. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin’s disease. Blood. 1997;89:814-822.
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Volume : 15
Issue : 1
Pages : 133 - 135
DOI : 10.6002/ect.mesot2016.P21


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From the 1Iraqi Bone Marrow Transplantation Center, Baghdad, Iraq; and from 2Trieste, Italy
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Abdul Majeed A. Hammadi, ALYermook Teaching Hospital, Baghdad, Iraq
Phone: +964 78 0342 0174
E-mail: majeed51578@yahoo.co.uk