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Trends and outcomes-first 100 bone marrow transplants at a Tertiary Care Center in Islamabad, Pakistan

Bone Marrow Transplantationvolume 53pages12281230 (2018) | Download Citation

Dear Editor,

Hematologic Malignancies arise in the hematopoietic stem cells and progenitor cells in the bone marrow or Lymph nodes which result in immature blood cells. The incidence of hematological malignancies is on the rise. Over 8% of all new diagnosed cancer patients in Europe in 2005 were found to have Leukemia, Hodgkin’s and non-Hodgkin’s lymphoma and myeloma [1]. In 2007 an estimated 135,000 new cases of hematologic malignancies were reported in the US [2].

Treatment for hematological malignancies involves radiation, immunotherapy, chemotherapy, and stem cell transplantation. Hematopoietic stem cell transplant (HSCT) is a definite therapy for many curable high-risk hematological disorders.

HSCT program at our center commenced in 2009 and up till now 100 stem cell transplant procedures have been carried out. Our center is one of four centers currently offering HSCT in Pakistan. Matched related donor allogenic and haplo identical transplants are carried out. We are in process of starting a marrow donor registry.

We tried to analyze outcomes of our center to compare them to the region and the world. This study was conducted after approval from the Institutional review board and ethics committee. First 100 patients who underwent HSCT at our center were included in the study. Medical record charts of these patients were reviewed and information related to demographics, indications for transplant, chemotherapy and drug regimens, remission status, stem cell source, engraftment, time incidence of acute graft-versus-host disease (GvHD) and any other complication developed was recorded. The progression-free survival (PFS) and overall survival (OS) were calculated till the day of last follow-up visit.

A total of 100 bone marrow transplants were performed at the Shifa International Hospital from 2009 to June 2017. Out of these 46 were autologous, and 54 were allogenic. There were 72 males and 28 females. Demographics have been shown in Table 1. 12% transplants were done for benign diseases while 88% of the transplants were carried out due to malignant hematological conditions.

Table 1 Patient demographics

The mean age at time of transplant was 34 ± 15 years (range 1–67 years). A total of 89 patients belonged to adult age group (age >15 years) and 11 patients belonged to the pediatric age group (age <15 years).

The major indications for HSCT around the world are AML, ALL, lymphoma, and myeloma. The indications for transplant at our center have been described in Fig. 1. According to the US data published by CIBMTR in 2014 the most common indications for HSCT in the US in 2014 were myeloma and lymphoma, accounting for 56% of all HCTs [3]. However, the major indications for HSCT in Pakistan according to a study in 2007 were aplastic anemia and B-Thalassemia [4].

Fig. 1
Fig. 1

Indications for bone marrow transplant; (MDS Myelodysplastic syndrome, CML chronic myeloid leukemia, DLBCL diffuse large B- cell lymphoma, ALCL anaplastic large cell lymphoma)

In our study the main indications were ALL (17%) followed by Hodgkins Lymphoma (11%), making our cohort more similar to western patients undergoing transplant.

Conditioning regimens for 43% of patients could not be retrieved from available medical records. From available data patients with ALL received busalfan and cyclophosphamide (BuCy) and fludarabine and melphalan (FluMel), patients with HL received carmustine, etoposide, cytarabine, and melphalan(BeEAM), patients with AML received busalfan, fludarabine, and melphalan (BuFluMel), BuCy and FluMel, and patients with NHL received FluMel, and BeEAM conditioning regimens. Patients with aplastic anemia were given fludarabine and cyclophosphamide(FluCy) and those with thalassemia were given BuCy conditioning regimens.

Peripheral blood was the source of stem cells in 52% of the donors and bone marrow was used as source in 1 patient only. Stem cell source of 47 donors could not be retrieved from medical records but most were likely stem cells. In 31 patients recombinant granulocyte-colony stimulating factor was used to mobilize stem cells. 

At time of transplant 14 patients were in complete remission (CR), 19 were in partial remission, 1 was in very good partial remission, 7 were in CR1, 1 was in CR2 and 3 were in CR3. All  stem cell donors were matched siblings and 2 were haplo identical matched to the recipients.

All patients were given an antibiotic prophylactic regimen containing acyclovir, voriconazole, levofloxacin, and trimethoprim sulfamethoxazole. For GvHD prophylaxis cyclosporine, methotrexate, mycophenolate mofetil were used either individually or in combination with each other.

The mean time for neutrophil recovery was 17.5 days while mean time for platelet engraftment was 18.2 days. The mean time for neutrophils engraftment and platelet engraftment for autologous transplant was 17.8 and 18.5 days, respectively. For Allogenic the mean neutrophil engraftment time was 17.3 days and platelet engraftment took 18.2 days on average.

Incidence of acute GvHD and chronic GvHD was 14% and 7%, respectively. Acute GvHD was treated with steroids in 12 patients while the details of those remaining were not available medical records.

Most common complications that occurred in the post transplant period were mucositis, neutropenic fever, constipation, diarrhea, vomiting, cough, and shortness of breath.

TRM is defined as mortality occurring within first 100 days of transplant due to causes not related to underlying disease [5]. In our review the overall TRM was 21%. The TRM for autologous transplant was 15.2% and that for allogenic was 25.9%. In a previous study done at another regional center, AFBMTC reported TRM for allogenic transplants to be 19.5% [6]. Studies conducted at other centers in Pakistan have shown TRM of 32.6% and 14.3% for Allogenic BMT. A multi centered study conducted by EBMT reported a TRM of 14.7% for allogenic transplants after analyzing data from several countries, including Finland and Italy [7].

The OS at a follow-up of 2 years was 60% and plateaued to 55% at 3 years and beyond over a 7 year follow-up. Median PFS was 1592 days (SD ± 144) with best seen for Thalassemia and worst for Germ Cell Tumors (Fig. 2).

Fig. 2
Fig. 2

Kaplan–Meier charts showing OS and PFS at our center. a Disease wise PFS, b overall survival, c OS according to type of transplant

We are currently enrolled in CIBMTR. We aim to set-up Pakistan Marrow Donor Registry to perform matched unrelated donor transplant, exchange donors, and initiate cord blood transplants, introduce CART therapy and collaborate with international investigators with better database documentation.

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    Majhail NS, Farnia SH, Carpenter PA, Champlin RE, Crawford S, Marks DI, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:1863–9.

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    Schmitz N, Beksac M, Bacigalupo A, Ruutu T, Nagler A, Gluckman E, et al. Filgrastim-mobilized peripheral blood progenitor cells versus bone marrow transplantation for treating leukemia: 3-year results from the EBMT randomized trial. Haematologica. 2005;90:643–8.

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Affiliations

  1. Shifa College of Medicine, Shifa Tameer-E-Millat University, Islamabad, Pakistan

    • Fahad Mushtaq
    •  & Umer Farooq
  2. Shifa International Hospital (SIH), Islamabad, Pakistan

    • Kamran Rashid
    • , Ayesha Junaid
    • , Tahir Aziz
    • , Yasir Iqbal
    • , Shawana Kamran
    • , Waseem Sajjad
    •  & M. Ayaz Mir
  3. Shifa Clinical Research Center (SCRC), Islamabad, Pakistan

    • Danish Khan

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The authors declare that they have no conflict of interest.

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Correspondence to M. Ayaz Mir.

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https://doi.org/10.1038/s41409-018-0210-9